Single coronary artery arising from the right sinus of Valsalva.
Single coronary artery (SCA) is a rare congenital anomaly in which the entire coronary system arises from a solitary ostium. A 65-year-old male with a history of diabetes mellitus, hypertension, and hyperlipidemia was admitted with exertional angina pectoris of new onset. His physical examination, hemogram, thyroid function tests, chest X-ray, electrocardiogram, and transthoracic echocardiogram were normal. In treadmill exercise test, the patient could not reach submaximal heart rate due to fatigue. Coronary angiography revealed an SCA arising from the right sinus of Valsalva (type R-IIA). The left coronary artery (LCA) coursed anteriorly in front of the right ventricular outflow tract and gave off branches for the left anterior descending and left circumflex (LCx) arteries. A mild diffuse nonobstructive atherosclerotic lesion was also detected in the LCx. The entire SCA and the anterior course of the LCA in relation to the great vessels were further displayed by 16-row multislice computed tomography. The atherosclerotic lesion was not eligible for percutaneous intervention and the patient was scheduled for medical therapy with recommendation of risk factor modification.


[Clinical testing of hemo- and plasmosorption on the Aktilen hemosorbent].
The authors make an analysis of using hemosorption and plasmasorption in 43 patients with the help of fibrous sorbent "Actilen". The developed methods have a pronounced detoxicating immunocorrecting, rheocorrecting effect, exert mild aggressive influence on blood and can be used in treatment of surgical, therapeutic and infectious diseases. The following advantages are noted: high sorption and kinetic characteristics of the sorbent, domestic devices and materials, small volume of the filling of mass transfer devices, low cost.


Mothers' experience of having children with diabetes.
Diabetes is a major health problem, which has a wide prevalence in the world. There is no sign of its stopping, but it is increasing. Diabetes in children is three to four times more common than other childhood diseases. Diagnosis of diabetes for children causes emotional responses in parents and family members. Interventions for children with diabetes involve the family, child, and professionals including physicians, nurses, and nutritionist. Self-care is difficult without direct parents' participation. According to studies, burden of diabetes for mothers is more than for fathers. This study aimed to explore mothers' experience of children with diabetes. This is a qualitative content analysis. Study population was recruited through purposeful sampling. Eleven mothers who have a child with diabetes and referring to the "Glands and Metabolism Research Center" and "Al-Zahra Hospital" were selected. Participants were aged 28 to 42 years. Data gathering was done through deep interviews with participants in 2007 that was tape-recorded. Mean average of interviews was 45 minutes. Data analysis was done using conventional qualitative content analysis. Participants' experience was classified in the two main concepts including reaction at the time of diagnosis and disease consequences for mothers. Mothers of children with diabetes expressed some reactions at the time of diagnosis, which was mainly due to lack of information, and lack of attention to their needs at the time of diagnosis, especially it was due to the sudden diagnosis and lack of enough opportunities for mothers to accept the disease. The disease causes some consequences for mothers that affect their lives. Therefore, it is necessary to consider the needs of families of children with diabetes and to provide support and sufficient information about their child's illness for them.


Comparison of 30-Day Postoperative Outcomes after Laparoscopic vs Robotic Colectomy.
The robotic platform has been used increasingly to perform colorectal surgery. The benefits of robotic colectomy when compared with laparoscopic colectomy have not been definitively established. A retrospective review of the NSQIP database was performed on patients undergoing elective laparoscopic or robotic colectomy in 2013. Demographic characteristics, length of stay, operative time, and 30-day postoperative complications were compared between the 2 groups. Of the 17,774 colectomies performed during the study period, 11,267 (63.4%) were performed laparoscopically and 653 (3.7%) were performed robotically. In comparison with laparoscopic colectomy, robotic colectomy was associated with increased operative time (233 vs 180 minutes; p < 0.01) and decreased length of stay (5.04 vs 6.06 days; p < 0.01). There was no significant difference with respect to mortality (0.2% vs 0.4%; p < 0.312), anastomotic leak (3.4% vs 3.1%; p = 0.715), reoperation (4.9% vs 4.0%; p = 0.27), conversion (10.3% vs 12.2%; p = 0.13), or readmission (9.3% vs 8.7%; p = 0.593) rates. The differences in length of stay and operative time persisted in the right colectomy and left colectomy/sigmoid resection subgroup analysis with no difference in conversion rates. In this head-to-head comparison of laparoscopic colectomy and robotic colectomy, the majority of postoperative outcomes were equivalent, except for an increase in operative time and shorter length of stay in the robotic group. Robotic colectomy appears to be a safe option for minimally invasive colectomy, but additional studies are needed to elucidate whether it is cost-effective when compared with laparoscopic colectomy.


Cetuximab for treatment of advanced squamous cell carcinoma in solid organ transplant recipients.
Survival of solid organ transplant patients has been prolonged, leading to increased incidence of non-melanoma skin cancers. Metastatic squamous cell carcinoma is an increasing problem in these patients. This paper reviews the evidence available for the treatment of advanced squamous cell carcinoma with the epidermal growth factor receptor inhibitor, cetuximab.


Direction-specific postural instability in subjects with Parkinson's disease.
The purpose of this study was to determine whether and why subjects with Parkinson's disease (PD) have greater instability in response to specific directions of perturbations than do age-matched control subjects and how instability is affected by stance width. This study compared postural responses to 8 directions of surface translations in PD subjects and age-matched control subjects while standing in a narrow and wide stance. PD subjects were tested in their practical OFF state. A postural stability margin was quantified as the difference between peak center of pressure (CoP) and peak center of mass (CoM) displacement in response to surface translations. The control subjects maintained a consistent stability margin across directions of translations and for both narrow and wide stance by modifying rate of rise of CoP responses. PD subjects had smaller than normal postural stability margins in all directions, but, especially for backwards sway in both stance widths and for lateral sway in narrow stance width. The reduced stability margin in PD subjects was due to a slower rise and smaller peak of CoP in the PD subjects than in control subjects. Lateral postural stability was compromised in PD subjects by lack of trunk flexibility and backwards postural stability was compromised by lack of knee flexion, resulting in excessive displacements of the body CoM. Stability margins in PD subjects were related to their response on the pull test in the Unified Parkinson's Disease Rating Scale. Thus, PD patients have directionally specific postural instability due to an ineffective stiffening response and inability to modify their postural responses for changing postural demands related to direction of perturbation and initial stance posture. These results suggest that the basal ganglia, in addition to regulating muscle tone and energizing postural muscle activation, also are critical for adapting postural response patterns for specific biomechanical conditions.


Response of hematopoiesis to cyclophosphamide follows highly specific patterns in bone marrow and spleen.
Sublethal cyclophosphamide treatment induces unique regeneration patterns in bone marrow and the spleen of a mouse. Colony-forming units spleen (CFU-S)(day 8), CFU-granulocyte-macrophage (GM), nucleated cell counts, and their differentials in bone marrow, spleen, and peripheral blood were determined in mice treated with a single dose of cyclophosphamide. To study further the mechanisms underlying the unique patterns of hematopoietic regeneration after cyclophosphamide, mRNA levels for stem cell factor (SCF), Flt-3 ligand, and macrophage inflammatory factor (MIP)-1 alpha cytokines were determined in bone marrow and spleen. Granulocyte precursor cells were less depleted by cyclophosphamide compared to erythroid nucleated cells and lymphocytes both in bone marrow and spleen. Rapid expansion of granulopoietic cells increased the granulocytic/erythroid ratio significantly during regeneration. CFU-S in the bone marrow and the spleen showed different sensitivity in vivo but not in vitro to cyclophosphamide; CFU-GM were equisensitive in both sites. In bone marrow, an initial fast recovery of CFU-S and CFU-GM on days 2 to 3 was followed by a secondary deep decline in their numbers occurring between days 5 and 7. This decline was accompanied with a depression of CFU-S proliferation and with significantly increased CFU-S numbers in the peripheral blood. In the spleen, absolute CFU-S and CFU-GM numbers were increased several-fold at this time. Seven days after cyclophosphamide, the spleen contained 69% of the total body CFU-S compared to 4% in controls. Splenectomy did not abolish the secondary disease of CFU-S in the bone marrow, but it led to a marked elevation of circulating leukocytes and CFU-S. There was an eight-fold increase in the SCF mRNA level in the bone marrow 2 days after cyclophosphamide, corresponding with a high proliferation rate of CFU-S. No significant changes in mRNAs for Flt-3 ligand and MIP-1 alpha have been found. This in-depth analysis of murine hematopoietic responses to cyclophosphamide provides evidence for the complexity of the involved local and systemic regulations. This represents a significant challenge to experimental hematology, which could now be tackled with methods allowing the study of changes in the gene expression during cyclophosphamide-induced hematopoietic damage.


Coronavirus Disease 2019-COVID-19.
SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.


[Antioxidative function of katG gene in Rhizobium leguminosarum].
Catalase-peroxidase KatG can protect bacteria from damage of reactive oxygen species. This study investigated the antioxidative function of catalase - peroxidase gene katG in Rhizobium leguminosarum 3841. katG mutant strain of R. leguminosarum was constructed by homologous recombination. The wild type, katG mutant and complementary strain were challenged by oxidative stress and symbiotic ability. Under free - living conditions, the katG mutant exhibited no generation time extension. However, cells of the katG strain were deficient in consumption oj high concentrations of H2O2and were vulnerable after aquick exposure to H2O2. The real-time qRT-PCR results showec that katG was expressed independently of exogenous H2O2. In contrast, the katG mutant strain displayed higher expres, level of ohrB gene and lower expression level of grxC than the wild type. With regard to symbiotic capacities with Pisum sativum, the katG mutant was indistinguishable in root nodule nitrogenase activity and competition nodule ability from the wild type. However, katG gene was expressed significantly lower in bacteroids than that in free-living strains. Besides, the colonization of the pea rhizosphere by the katG mutant was impaired compared to that of the wild type. ThE deletion of katG had nosignificant effect in 3841 under the free-living and symbiosis condition but was essential ir antioxidation and colonization of the pea rhizosphere. Although katG could not be induced by H2O2, it still played acentra role in antioxidation and symbiotic nitrogen fixation by regulating the antioxidant genes such as ohrB and grxC.


Synthesis and phase width of quaternary selenides Pb4In(x)M(6-x)Se13 (M = Bi, x = 2.1-2.8; Sb, x = 2).
Quaternary selenides of Pb(4)In(x)M(6-x)Se(13) (M = Bi, x = 2.1-2.8; Sb, x = 2) were synthesized by solid-state methods, and their structures were determined from X-ray diffraction of single crystals. These compounds are isostructural with Pb(4)In(2)Bi(4)S(13) and crystallize in orthorhombic space group Pbam (No. 55) with Z = 4; the structure features a three-dimensional framework consisting of Z-shaped ribbon units and corner-sharing infinite one-dimensional [InSe(4)](infinity) chains running parallel to the c-axis, which are connected by Pb atoms to form a three-dimensional structure. Calculations of the band structure and measurements of Seebeck coefficient, electrical conductivity, and diffuse reflectance spectra confirm that these compounds are semiconductors with a narrow band gap. All compounds show semiconducting properties; the Seebeck coefficient of Pb(4)In(2.5)Bi(3.5)Se(13) is -180 microV/K at 295 K.


Multihormonal control of ob gene expression and leptin secretion from cultured human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity.
The direct role of hormones on leptin synthesis has not yet been studied in cultured adipose cells or tissue from lean and obese subjects. Moreover, this hormonal regulation has never been addressed in human visceral fat, although this site plays a determinant role in obesity-linked disorders. In this study, we investigated the hormonal control of ob expression and leptin production in cultured visceral adipose tissue from lean and obese subjects. We more particularly focused on the interactions between glucocorticoids and insulin. We also briefly tackled the role of cAMP, which is still unknown in man. Visceral (and subcutaneous) adipose tissues from eight obese (body mass index, 41 +/- 2 kg/m2) and nine nonobese (24 +/- 1 kg/m2) subjects were sampled during elective abdominal surgery, and explants were cultured for up to 48 h in MEM. The addition of dexamethasone to the medium increased ob gene expression and leptin secretion in a time-dependent manner. Forty-eight hours after dexamethasone (50 nmol/L) addition, the cumulative integrated ob messenger ribonucleic acid (mRNA) and leptin responses were, respectively, approximately 5- and 4-fold higher in obese than in lean subjects. These responses closely correlated with the body mass index. The stimulatory effect of the glucocorticoid was also concentration dependent (EC50 = approximately 10 nmol/L). Although the maximal response was higher in obese than in lean subjects, the EC50 values were roughly similar in both groups. Unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression and leptin secretion. Singularly, insulin even inhibited the dexamethasone-induced rise in ob mRNA and leptin release. This inhibition was observed in both lean and obese subjects, whereas the expected stimulation of insulin on glucose metabolism and the accumulation of mRNA species for the insulin-sensitive transporter GLUT4 and glyceraldehyde-3-phosphate dehydrogenase occurred in lean patients only. This inhibitory effect was already detectable at 10 nmol/L insulin and was also observed in subcutaneous fat. Although a lowering of intracellular cAMP concentrations is involved in some of the effects of insulin on adipose tissue, this cannot account for the present finding, because the addition of cAMP to the medium also decreased ob mRNA and leptin secretion (regardless of whether dexamethasone was present). In conclusion, glucocorticoids, at physiological concentrations, stimulated leptin secretion by enhancing the pretranslational machinery in human visceral fat. This effect was more pronounced in obese subjects due to a greater responsiveness of the ob gene and could contribute to the metabolic abnormalities associated with central obesity by para/endocrine actions of hyperleptinemia on adipocytes and liver. Unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression and leptin secretion, and even prevented the positive response to dexamethasone by a cAMP-independent mechanism that remained functional despite insulin resistance.


Changes in countermovement jump performance and subjective readiness-to-train scores following a simulated soccer match.
The study investigated whether countermovement jump (CMJ) metrics and subjective responses to a readiness-to-train questionnaire (RTT-Q) tracked simulated match-induced acute fatigue. This was a randomized cross-over repeated measures study. Participants were assigned into one of two groups; CONTROL or LIST. The LIST group performed the Loughborough Intermittent Shuttle Run (LIST), which was designed to simulate the demands of a soccer match. The CONTROL performed light physical activity at an intensity of <65% of maximal heart rate. Each group performed three CMJ's and completed an RTT-Q before (PRE), and again at 24 and 48 h after the LIST and/or CONTROL interventions. At 24 h there were significant differences in RTT-Q answers between the Pre and 24 h for the LIST group for questions; "Do you feel physically strong today?" and "Do you have muscle soreness today?" (p = 0.02 and 0.0008, respectively). The questions "Do you feel mentally strong today?" and "Do you have muscle soreness today?" (p = 0.02 and p = 0.0001 respectively) were the only questions that had a significant difference between Pre and 48 h for the LIST group. None of the CMJ metrics (LIST or CONTROL) changed significantly at any stage of the experiment. Although fatigue was detected by changes in the RTT-Q at 24 and 48 h after the LIST, none of the CMJ metrics changed. These findings suggest that subjective measures are more sensitive to low-level fatigue than objective measures, thus effective monitoring should include both.


Brain nitric oxide and its dual role in neurodegeneration/neuroprotection: understanding molecular mechanisms to devise drug approaches.
Nitric oxide (NO) has been established as an important messenger molecule in various steps of brain physiology, from development to synaptic plasticity, learning and memory. However, NO has also been viewed as a major agent of neuropathology when, escaping controlled production it may directly or indirectly promote oxidative and nitrosative stress. The exact borderline between physiological, and therefore neuroprotective, and pathological, and therefore neurodegenerative, actions of NO is a matter of controversy among researchers in the field. This is reflected in the present status of drug research, that is focused on finding ways to block NO production, and therefore limit neuropathology, as well as on finding ways to increase NO availability and therefore elicit neuroprotection. As an unavoidable consequence, both classes of drugs are reported to have neurodegenerative or neuroprotective effects, depending on the models in which they are tested. Aim of the present paper is to provide the reader with a survey, as much complete as possible, on the main aspects of NO biology, from biochemistry and chemical reactivity to the molecular signals elicited in neural cells target of its neurodegenerative or neuroprotective action. In doing that, many controversial aspects related to basic biology and to neuropathology of NO are taken into account. In the final sections, main classes of drugs able to interfere with NO physiopathology are examined, in order to try to devise possible directions for future NO-based therapeutical strategies.


Model-based QSAR for ionizable compounds: toxicity of phenols against Tetrahymena pyriformis.
The previously described pseudo-equilibrium model for kinetics of distribution of extraneous chemicals in biological systems has been used for the development of the QSAR equation expressing toxicity of phenols against Tetrahymena pyriformis as a non-linear function of their hydrophobicity and acidity. The model assumes binding of all the tested compounds to a single class of the receptors (i.e., it does not discriminate between possible narcotic and respiratory uncoupling modes of action of phenols) with the association constant related to the electronic structure of the molecules rather than to their hydrophobicity. Non-linear regression analysis revealed satisfying agreement between the model and published biological data measured after a single dose.


A refined algorithm for multisensor image registration based on pixel migration.
Multimodality image registration via pixel migration is a powerful approach. However, it suffers from a serious problem--the global maximum on the sum of squared gradient magnitude (SSG) surface does not correspond to the correct solution of registration. To solve the problem, we partition the search space into feasible and infeasible regions. The genetic algorithm (global optimizer) is used to obtain a good initial estimate of registration parameters and followed by a fast refining with Powell's approach (local optimizer). The experimental results demonstrate that the use of this modified pixel migration algorithm on multisensor image registration is very effective.


Utilizing Behavioral Economics to Understand Adherence to Physical Activity Guidelines Among a Low-Income Urban Community.
Behavioral economics studies have found that individuals with more patient time preferences (ie, greater willingness to forgo current costs for future benefits) are more likely to save money. Although research has observed significant relationships between time preferences and health-promoting behaviors, scant evidence exists with physical activity as an outcome. We examined the association between monetary saving behaviors and physical activity among adults of low-income who reside in an urban community. Specifically, we assessed the relationship between saving behaviors (checking/saving account, monthly savings, and planning family finances), and future orientation to physical activity as a dichotomous (meeting guidelines) and continuous (total and domain specific) endpoint. In multivariable regression, being future-oriented and having a checking/saving account were related to a 1.3 and 2.1 times higher (respectively) likelihood of meeting physical activity guidelines (P < .05). When examining physical activity continuously, all measures were significantly related to leisure-time activity (P < .05). Our study findings establish a relationship between future time preferences and increased levels of physical activity among low-income adults. Future research should prospectively explore the efficacy of various schemes that help individuals overcome impatient time preferences to determine a causal relationship.


Is irritable bowel syndrome a low-grade inflammatory bowel disease?
Irritable Bowel Syndrome (IBS) is multifactorial in its etiology and heterogeneous in its clinical presentation and pathogenesis. It is recognized that inflammation plays an important role in symptom generation, at least in a subset of patients with IBS. Previous gastroenteritis has been identified as the most important risk factor for IBS, and several studies reported that a substantial proportion of patients with gastrointestinal infection develops IBS symptoms,which can persist for several years. Recent studies have demonstrated that a proportion of IBS patients without any history of enteritis has signs of immune activation in the gut. There is clinical overlap between IBS and inflammatory bowel disease (IBD), with IBS-like symptoms frequently reported in patients before the diagnosis of IBD, and a higher than expected percentage reports of IBS symptoms in patients in remission from established IBD. Thus,these conditions may coexist with a higher than expected frequency, or may exist on a continuum, with IBS and IBD at different ends of the same spectrum. This article examines these relation-ships using immune activation and inflammation as a common pathogenic process to IBD and a subset of IBS patients.


The effectiveness of a short-term group music therapy intervention for parents who have a child with a disability.
The positive relationship between parent-child interactions and optimal child development is well established. Families of children with disabilities may face unique challenges in establishing positive parent-child relationships; yet, there are few studies examining the effectiveness of music therapy interventions to address these issues. In particular, these studies have been limited by small sample size and the use of measures of limited reliability and validity. This study examined the effectiveness of a short-term group music therapy intervention for parents of children with disabilities and explored factors associated with better outcomes for participating families. Participants were 201 mother-child dyads, where the child had a disability. Pre- and post-intervention parental questionnaires and clinician observation measures were completed to examine outcomes of parental wellbeing, parenting behaviors, and child development. Descriptive data, t-tests for repeated measures and a predictive model tested via logistic regression are presented. Significant improvements pre to post intervention were found for parent mental health, child communication and social skills, parenting sensitivity, parental engagement with child and acceptance of child, child responsiveness to parent, and child interest and participation in program activities. There was also evidence for high parental satisfaction and that the program brought social benefits to families. Reliable change on six or more indicators of parent or child functioning was predicted by attendance and parent education. This study provides positive evidence for the effectiveness of group music therapy in promoting improved parental mental health, positive parenting and key child developmental areas.


Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications.
Tyrosinase (TYR, E.C. 220.127.116.11), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the ortho-hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR activity and their biomedical applications. The design strategies of various TYR substrates, alongside with several lists of all reported biochemical assays for sensing TYR including analytical conditions and kinetic parameters, are presented for the first time. Additionally, the biomedical applications and future perspectives of these optical assays are also highlighted. The information and knowledge presented in this review offer a group of practical and reliable assays and imaging tools for sensing TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases.


Transfer of probenecid and cephalexin into breast milk.
To report a case of the transfer of probenecid and cephalexin into human milk. A breast-fed infant of a 30-year-old woman being treated with oral probenecid and cephalexin for a breast infection developed severe diarrhea and associated symptoms. To investigate whether the maternal drug treatment was causative, milk was collected over a dose interval at steady-state, and concentrations of probenecid and cephalexin were measured by HPLC. The average concentrations of probenecid and cephalexin in milk were 964 and 745 microg/L, respectively, corresponding to absolute and relative infant doses of 145 microg/kg/day and 0.7% for probenecid and 112 mug/kg/day and 0.5% for cephalexin. The infant's adverse effects were rated as possible for probenecid and probable for cephalexin based on the Naranjo probability scale. On the basis of the calculated relative infant doses for both probenecid and cephalexin in milk and the notional 10% level of concern for infant exposure, neither drug would be expected to cause significant systemic effects. However, local adverse effects, notably diarrhea, were observed. The Naranjo probability scale rating suggested that cephalexin was more likely than probenecid to be the cause of the infant's diarrhea. When using cephalexin/probenecid to treat breast infections in lactating women, clinicians should anticipate the possibility of adverse gastrointestinal effects in the breast-fed infant.


Gasterophilosis: a major cause of rectal prolapse in working donkeys in Ethiopia.
A retrospective study was conducted to investigate the cause of rectal prolapse in working donkeys in Ethiopia. Analysis of data on rectal prolapse cases obtained from the Donkey Health and Welfare Project clinic at the School of Veterinary Medicine, Addis Ababa University, from 1995 to 2004 revealed that 83.6% (n = 177) of the cases were associated with Gasterophilus nasalis. The rest 10.7% and 5.7% were associated with work-related (overloading) cause and diarrhoea, respectively. The mean and median numbers of G. nasalis recovered from the rectum of infected donkeys were 66 and 64, respectively, with a range of 2-195. Over 100 G. nasalis larvae were recovered from the rectum of 22% of the donkeys. Circular demarcated ulcer-like and deep circumferential pits or ring-like mucosal lesions were found at the larval attachment sites. G. nasalis infection and the associated rectal prolapse were observed year round. However, the intensity of rectal larval infection and incidence of rectal prolapse were significantly higher during the rainy season (P < 0.01). Age and sex of the donkeys had no significant effect on the intensity of rectal larval infection and incidence of rectal prolapse (P > 0.05).


Exploring racial influences on flu vaccine attitudes and behavior: Results of a national survey of White and African American adults.
Racial disparities in adult flu vaccination rates persist with African Americans falling below Whites in vaccine acceptance. Although the literature has examined traditional variables including barriers, access, attitudes, among others, there has been virtually no examination of the extent to which racial factors including racial consciousness, fairness, and discrimination may affect vaccine attitudes and behaviors. We contracted with GfK to conduct an online, nationally representative survey with 819 African American and 838 White respondents. Measures included risk perception, trust, vaccine attitudes, hesitancy and confidence, novel measures on racial factors, and vaccine behavior. There were significant racial differences in vaccine attitudes, risk perception, trust, hesitancy and confidence. For both groups, racial fairness had stronger direct effects on the vaccine-related variables with more positive coefficients associated with more positive vaccine attitudes. Racial consciousness in a health care setting emerged as a more powerful influence on attitudes and beliefs, particularly for African Americans, with higher scores on racial consciousness associated with lower trust in the vaccine and the vaccine process, higher perceived vaccine risk, less knowledge of flu vaccine, greater vaccine hesitancy, and less confidence in the flu vaccine. The effect of racial fairness on vaccine behavior was mediated by trust in the flu vaccine for African Americans only (i.e., higher racial fairness increased trust in the vaccine process and thus the probability of getting a flu vaccine). The effect of racial consciousness and discrimination for African Americans on vaccine uptake was mediated by perceived vaccine risk and flu vaccine knowledge. Racial factors can be a useful new tool for understanding and addressing attitudes toward the flu vaccine and actual vaccine behavior. These new concepts can facilitate more effective tailored and targeted vaccine communications.


Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.
Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).


Risk Assessment and Recommendations for Forester Exposure to Hymenoptera.
Ants, bees, hornets, wasps, and yellow jackets (insects in Order Hymenoptera) are potentially a serious concern to outdoor workers, as the venom from their stings can cause life-threatening allergic reactions. This study assessed the impacts of Hymenoptera stings and related worker training regimes of forestry workers across the United States (US). A survey was distributed to nearly 2,000 outdoor workers in the forestry industry from four US regions (South, West, Northeast, and Midwest). Ants are a primary concern in the South, with >75% of participants reporting ant stings within the last 5 years. Bees, hornets, wasps, and yellow jackets are a concern for surveyed foresters in all US regions, with 60-70% and 75-93% of participants, respectively, having been stung by bees or hornets/wasps/yellow jackets within the last 5 years. Despite such a large number of participants experiencing stings, nearly 75% of participants were not concerned about being stung or their reaction to stings. Approximately, 70% of participants reported not having received any safety training related to Hymenoptera from their employers. No significant difference was shown in the number of foresters stung at work between safety trained and non-safety trained participants. However, it was significantly more likely for participants to carry a first aid kit if they had received Hymenoptera safety training. Consequently, more comprehensive and frequent training should be considered to help reduce risk of exposure to Hymenoptera.


Central auditory development in children with cochlear implants: clinical implications.
A common finding in developmental neurobiology is that stimulation must be delivered to a sensory system within a narrow window of time (a sensitive period) during development in order for that sensory system to develop normally. Experiments with congenitally deaf children have allowed us to establish the existence and time limits of a sensitive period for the development of central auditory pathways in humans. Using the latency of cortical auditory evoked potentials (CAEPs) as a measure we have found that central auditory pathways are maximally plastic for a period of about 3.5 years. If the stimulation is delivered within that period CAEP latencies reach age-normal values within 3-6 months after stimulation. However, if stimulation is withheld for more than 7 years, CAEP latencies decrease significantly over a period of approximately 1 month following the onset of stimulation. They then remain constant or change very slowly over months or years. The lack of development of the central auditory system in congenitally deaf children implanted after 7 years is correlated with relatively poor development of speech and language skills [Geers, this vol, pp 50-65]. Animal models suggest that the primary auditory cortex may be functionally decoupled from higher order auditory cortex due to restricted development of inter- and intracortical connections in late-implanted children [Kral and Tillein, this vol, pp 89-108]. Another aspect of plasticity that works against late-implanted children is the reorganization of higher order cortex by other sensory modalities (e.g. vision). The hypothesis of decoupling of primary auditory cortex from higher order auditory cortex in children deprived of sound for a long time may explain the speech perception and oral language learning difficulties of children who receive an implant after the end of the sensitive period.


INFECTION OF WHITE SWISS MICE WITH AIRBORNE CRYPTOCOCCUS NEOFORMANS.
Smith, C. D. (Communicable Disease Center, Kansas City, Kansas), R. Ritter, H. W. Larsh, and M. L. Furcolow. Infection of white Swiss mice with airborne Cryptococcus neoformans. J. Bacteriol. 87:1364-1368. 1964.-A group of 39 white Swiss male mice were allowed to run 3 days on previously sterilized soil that had been seeded with Cryptococcus neoformans 1 year previously. It was determined that the soil contained an average of 1.6 x 10(6) viable yeast cells per ml. The mice were observed for 24 weeks, at which time the survivors were necropsied. The total mortality rate during this period was 44%; 67% of the mice had positive cultures, including all who had a fatal infection. Two additional experiments were done with the same strain with the use of aerosols produced by a Henderson apparatus. In experiment 1, 39 mice received 11,000 viable cells each; in experiment 2, 40 mice received 14,622 viable cells. Both groups of mice showed similar mortality rates, with a total of 77% dead after 20 weeks in experiment 1, and 80% in experiment 2. All of the mice in experiment 1 had positive cultures, as did 95% of the mice in experiment 2.


Reaction-diffusion spatial modeling of COVID-19: Greece and Andalusia as case examples.
We examine the spatial modeling of the outbreak of COVID-19 in two regions: the autonomous community of Andalusia in Spain and the mainland of Greece. We start with a zero-dimensional (0D; ordinary-differential-equation-level) compartmental epidemiological model consisting of Susceptible, Exposed, Asymptomatic, (symptomatically) Infected, Hospitalized, Recovered, and deceased populations (SEAIHR model). We emphasize the importance of the viral latent period (reflected in the exposed population) and the key role of an asymptomatic population. We optimize model parameters for both regions by comparing predictions to the cumulative number of infected and total number of deaths, the reported data we found to be most reliable, via minimizing the ℓ^{2} norm of the difference between predictions and observed data. We consider the sensitivity of model predictions on reasonable variations of model parameters and initial conditions, and we address issues of parameter identifiability. We model both the prequarantine and postquarantine evolution of the epidemic by a time-dependent change of the viral transmission rates that arises in response to containment measures. Subsequently, a spatially distributed version of the 0D model in the form of reaction-diffusion equations is developed. We consider that, after an initial localized seeding of the infection, its spread is governed by the diffusion (and 0D model "reactions") of the asymptomatic and symptomatically infected populations, which decrease with the imposed restrictive measures. We inserted the maps of the two regions, and we imported population-density data into the finite-element software package COMSOL Multiphysics®, which was subsequently used to numerically solve the model partial differential equations. Upon discussing how to adapt the 0D model to this spatial setting, we show that these models bear significant potential towards capturing both the well-mixed, zero-dimensional description and the spatial expansion of the pandemic in the two regions. Veins of potential refinement of the model assumptions towards future work are also explored.


GTSE1 is a microtubule plus-end tracking protein that regulates EB1-dependent cell migration.
The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs) are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.


Clinical biomarker validation.
Biomarker assays have brought significant challenges to bioanalytical laboratories that historically have provided pharmacokinetic analytical services to the drug development industry. This has largely been due to two reasons: the lack of regulatory guidance in how to validate biomarker assays and the lack of scientists in bioanalytical laboratories with experience in this clinical arena. Since biomarkers have been measured for many decades in clinical laboratories globally, this article reviews the different types of analytical laboratories and their practices and case studies will demonstrate the potential outcomes of using biomarker assays in drug development when they are not validated correctly.


Long-Term Stability of the NIST Standard Ultrasonic Source.
The National Institute of Standards and Technology (NIST) Standard Ultrasonic Source (SUS) is a system comprising a transducer capable of output power levels up to 1 W at multiple frequencies between 1 MHz and 30 MHz, and an electrical impedance-matching network that allows the system to be driven by a conventional 50 Ω rf (radio-frequency) source. It is designed to allow interlaboratory replication of ultrasonic power levels with high accuracy using inexpensive readily available ancillary equipment. The SUS was offered for sale for 14 years (1985 to 1999). Each system was furnished with data for the set of calibration points (combinations of power level and frequency) specified by the customer. Of the systems that had been ordered with some calibration points in common, three were returned more than once to NIST for recalibration. Another system retained at NIST has been recalibrated periodically since 1984. The collective data for these systems comprise 9 calibration points and 102 measurements spanning a 17 year interval ending in 2001, the last year NIST ultrasonic power measurement services were available to the public. These data have been analyzed to compare variations in output power with frequency, power level, and time elapsed since the first calibration. The results verify the claim, made in the instruction sheet furnished with every SUS, that "long-term drift, if any, in the calibration of NIST Standard Sources is insignificant compared to the uncertainties associated with a single measurement of ultrasonic power by any method available at NIST."


Caring behaviour and its associated factors among nurses working at public hospitals in Gamo zone, southern Ethiopia: a cross-sectional study.
The purpose of this study was to assess nurses caring behaviours and its associated factors among nurses working at public hospitals in the Gamo zone of southern Ethiopia in 2022. Institutional based cross-sectional study was used. This study was conducted in five public hospitals in Gamo zone, southern Ethiopia. A total of 360 nurses of different level of qualification were included in this study using a proportional allocation method from the five hospitals and final study participants were recruited from all wards using a simple random sampling method from 20 June to 20 July 2022. Caring behaviour was assessed using 24 standardised Caring Behaviour Inventory (CBI) scales. Data were collected using a structured questionnaire and, analysed using the logistic regression method, and those variables with a p value of <0.05 in multivariable analysis were considered statistically significant. The overall percentage of nurse caring behaviour in this study was 53.3%. Most of the respondents practiced technical aspects of caring behaviour rather than psychosocial aspects of caring. Being married (adjusted OR (AOR)=0.027 (0.003-0.263), having work experience of (0-5 years) (AOR=5.547 (1.42-21.64)), (6-10 years) (AOR=8.693 (2.317-32.6), being satisfied with motivation and prospect (AOR=0.473 (0.290-0.770)) and being satisfied with the nursing profession (AOR=1.716 (1.065-2.765) were significantly associated with nurses caring behaviour. The proportion of nurses with a good caring behaviour found in this study was relatively poor. Being married, having lower work experience, being satisfied with motivation and prospects, and nursing profession were associated with nurses caring behaviour. This study recommends the need to focus on including caring behaviour courses in the nursing curriculum and training nurses focusing on those with a few experiences on the meaning and importance of caring behaviour.


An Integrated Children Disease Prediction Tool within a Special Social Network.
This paper proposes a social network with an integrated children disease prediction system developed by the use of the specially designed Children General Disease Ontology (CGDO). This ontology consists of children diseases and their relationship with symptoms and Semantic Web Rule Language (SWRL rules) that are specially designed for predicting diseases. The prediction process starts by filling data about the appeared signs and symptoms by the user which are after that mapped with the CGDO ontology. Once the data are mapped, the prediction results are presented. The phase of prediction executes the rules which extract the predicted disease details based on the SWRL rule specified. The motivation behind the development of this system is to spread knowledge about the children diseases and their symptoms in a very simple way using the specialized social networking website www.emama.mk.


Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell 1 dominant state.
Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy. Using a C57BL/6 mouse model, OK-432 was found to induce multiple cytokines including the Th1 polarizing cytokine IL-12. Expression of IL-12 protein by murine splenocytes was restricted to macrophages and B cells and led to high levels of IFN-gamma production from both CD4+ and CD8+ T cells. Of the Th2 cytokines IL-4 and IL-10, only IL-10 protein was detected and originated primarily from the adherent cell population. Its expression was delayed relative to IL-12. A similar pattern of cytokine induction was observed from human PBMCs. OK-432-driven IFN-gamma production was inhibited by anti-IL-12 Ab, anti-IL-2 Ab, anti-TNF-alpha Ab, and anti-IL-2R alpha Ab, suggesting that IFN-gamma production from Th1 cells is induced by the cooperation action of these cytokines through the IL-2R alpha pathway. When compared with another widely used immunopotentiator bacillus Calmette-Guérin (BCG), OK-432 was a stronger IL-12 and IFN-gamma inducer. Furthermore, the mechanism of IFN-gamma induction by OK-432 differed from BCG in that coincident granulocyte-macrophage CSF and IL-1 expression played little to no role. These results suggest that OK-432 is a potent multicytokine inducer, specifically a strong inducer of IL-12, and that OK-432 may exert its antitumor effect by promoting a Th1-dominant state.


Development of a highly accurate nomogram for prediction of the need for exploration in patients with renal trauma.
To develop and validate a nomogram for predicting the need for renal exploration after renal trauma. From 1995 through 2004, 419 consecutive patients presented to our institution with traumatic renal injury. All were randomly divided into a development (50%, n = 210) and a split sample validation cohort (50%, n = 209). Logistic regression models were used to develop a nomogram for prediction of the need for renal exploration after renal trauma. Internal (200 bootstrap resamples) and 50% split sample validations were performed. Overall, 89 patients (21.2%) underwent renal exploration, from which 60.7% (54 of 89) underwent nephrectomy and 39.3% (35 of 89) underwent renorrhaphy. Nine percent of patients with grade II injury underwent renal exploration, 16% with grade III injuries, 41% with grade IV injuries, and 100% of grade V injuries. The kidney injury scale, the mechanism of injury, the need for transfusion, blood urea nitrogen level, and serum creatinine represented the most informative predictors and were included in the nomogram. The split sample accuracy of the nomogram for prediction of the need for renal exploration was 96.9%. It significantly (p < 0.001) exceeded the accuracy of each of its components including the American Association for the Surgery of Trauma kidney injury scale (87.7%). The nomogram generates highly accurate and reproducible predictions of the probability for renal exploration according to our decision-making. It could help standardize the management of patients with renal trauma (i.e., inclusion criteria for clinical trials) and serves as a proof-of-principle that predictive tools can be applied to the trauma setting. Its use may improve the management of renal trauma patients at institutions with limited trauma experience.


Drug-Related Adverse Events of Osteoporosis Therapy.
Postmenopausal osteoporosis is associated with microarchitectural deterioration and increased risk of fracture. Osteoporosis therapy effectively reduces the risk of vertebral, nonvertebral, and hip fracture and has been associated with increased survival. Currently approved treatments for osteoporosis include bisphosphonates, denosumab, selective estrogen receptor modulators, and teriparatide. This article reviews the adverse events of therapy associated with these medical interventions. Hormone replacement therapy is not included, because it is no longer indicated for the treatment of osteoporosis in all countries. Calcitonin and strontium ranelate are also not included, because their indication for osteoporosis has recently been limited or withdrawn.


Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites.
The TAZ1 domain of the homologous transcriptional coactivators CREB-binding protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1alpha) and thereby attenuating the cellular response to low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1 domain bound to the activation domain of CIT-ED2. The structure of TAZ1, consisting of four alpha-helices (alpha(1)-alpha(4)) stabilized by three zinc atoms, is very similar in the CITED2 and HIF-1alpha complexes. The activation domain of CITED2 is unstructured when free and folds upon binding, forming a helix (termed alpha(A)) and an extended structure that wraps around TAZ1. The CITED2 alpha(A) helix packs in the TAZ1 alpha(1)/alpha(4) interface, a site that forms weak interactions with the poorly defined aminoterminal alpha-helix of HIF-1alpha. CITED2 and HIF-1alpha both contain a four residue motif, LP(E/Q)L, which binds in the TAZ1 alpha(1)/alpha(2)/alpha(3) junction in each complex. The carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic contacts in the TAZ1 alpha(1)/alpha(3) interface in the site occupied by the HIF-1alpha alpha(B) helix. CITED2 does not bind at all to the TAZ1 site occupied by the HIF-1alpha carboxyl-terminal helix. The HIF-1alpha and CITED2 domains utilize partly overlapping surfaces of TAZ1 to achieve high affinity binding and to compete effectively with each other for interaction with CBP/p300; CITED2 and HIF-1alpha use these binding sites differently to maintain similar binding affinities in order to displace each other in a feedback loop during the hypoxic response.


Quantitative analysis of transient and sustained transforming growth factor-β signaling dynamics.
Mammalian cells can decode the concentration of extracellular transforming growth factor-β (TGF-β) and transduce this cue into appropriate cell fate decisions. How variable TGF-β ligand doses quantitatively control intracellular signaling dynamics and how continuous ligand doses are translated into discontinuous cellular fate decisions remain poorly understood. Using a combined experimental and mathematical modeling approach, we discovered that cells respond differently to continuous and pulsating TGF-β stimulation. The TGF-β pathway elicits a transient signaling response to a single pulse of TGF-β stimulation, whereas it is capable of integrating repeated pulses of ligand stimulation at short time interval, resulting in sustained phospho-Smad2 and transcriptional responses. Additionally, the TGF-β pathway displays different sensitivities to ligand doses at different time scales. While ligand-induced short-term Smad2 phosphorylation is graded, long-term Smad2 phosphorylation is switch-like to a small change in TGF-β levels. Correspondingly, the short-term Smad7 gene expression is graded, while long-term PAI-1 gene expression is switch-like, as is the long-term growth inhibitory response. Our results suggest that long-term switch-like signaling responses in the TGF-β pathway might be critical for cell fate determination.


Nitric oxide signaling via nuclearized endothelial nitric-oxide synthase modulates expression of the immediate early genes iNOS and mPGES-1.
Stimulation of freshly isolated rat hepatocytes with lysophosphatidic acid (LPA) resulted in LPA1 receptor-mediated and nitricoxide-dependent up-regulation of the immediate early genes iNOS (inducible nitric-oxide synthase (NOS)) and mPGES-1 (microsomal prostaglandin E synthase-1). Because LPA is a ligand for both cell surface and intracellular receptor sites and a potent endothelial NOS (eNOS) activator, we hypothesized that NO derived from activated nuclearized eNOS might participate in gene regulation. Herein we show, by confocal microscopy performed on porcine cerebral endothelial cells expressing native LPA1-receptor and eNOS and on HTC4 rat hepatoma cells co-transfected with recombinant human LPA1-receptor and fused eNOS-GFP cDNA, a dynamic eNOS translocation from peripheral to nuclear regions upon stimulation with LPA. Nuclear localization of eNOS and its downstream effector, soluble guanylate cyclase, were demonstrated in situ in rat liver specimens by immunogold labeling using specific antibodies. Stimulation of this nuclear fraction with LPA and the NO donor sodium nitroprusside resulted, respectively, in increased production of nitrite (and eNOS phosphorylation) and cGMP; these separate responses were also correspondingly blocked by NOS inhibitor L-NAME and soluble guanylate cyclase inhibitor ODQ. In addition, sodium nitroprusside evoked a sequential increase in nuclear Ca2+ transients, activation of p42 MAPK, NF-kappaB binding to DNA consensus sequence, and dependent iNOS RNA. This study describes a hitherto unrecognized molecular mechanism by which nuclear eNOS through ensuing NO modulates nuclear calcium homeostasis involved in gene transcription-associated events. Moreover, our findings strongly support the concept of the nucleus as an autonomous signaling compartment.


Jaw-muscle force and excursion scale with negative allometry in platyrrhine primates.
Platyrrhines span two orders of magnitude in body size and are characterized by diverse feeding behaviors and diets. While size plays an important role in primate feeding behavior and masticatory apparatus morphology, we know little about size-correlated changes in the force-generating (physiologic cross-sectional area; PCSA) and excursion/stretch (fiber length; Lf ) capabilities of the jaw-closing muscles in platyrrhines. We examined scaling relationships of the superficial masseter and temporalis muscles in 21 platyrrhine species. Previous work suggests that larger platyrrhines are at a mechanical disadvantage for generating bite forces compared with smaller platyrrhines. We hypothesize that scaling of jaw-muscle fiber architecture counters this size-correlated decrease in mechanical advantage. Thus, we predicted that jaw-muscle PCSAs and muscle weights scale with positive allometry while Lf s scale with negative allometry, relative to load-arm estimates for incisor/molar biting and chewing. Jaw-muscle PCSAs and Lf s appear to scale with negative allometry relative to load-arm estimates and body size. Negative allometry of jaw-muscle weights partially accounts for the size-correlated decreases in PCSA and Lf . Estimates of bite force also scale with negative allometry. Large-bodied platyrrhines (e.g., Alouatta) are at a relative disadvantage for generating jaw-muscle and bite force as well as jaw-muscle stretch, compared with smaller species (e.g., Callithrix). The net effect is that larger platyrrhines likely produce relatively smaller maximal bite forces compared with smaller taxa. Relative to small- and intermediate-sized platyrrhines, large-bodied platyrrhines feed on some of the least mechanically challenging foods, consistent with the size-correlated decrease in relative muscle and bite forces across the clade. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc. Am J Phys Anthropol 158:242-256, 2015. © 2015 Wiley Periodicals, Inc.


Assessment of learning and study strategies of university students in Qatar using an Arabic translation of the Learning and Study Strategies Inventory.
413 (119 men, 294 women) undergraduate university students in Qatar completed an Arabic version of the Learning and Study Strategies Inventory (LASSI) measuring Anxiety, Attitude, Concentration, Information Processing, Motivation, Self-testing, Selecting Main Ideas, Study Aids, Time Management, and Test Strategies. The students' learning and study strategies scores were similar to those reported in the literature. Factor analysis indicated the same general factors as in the original study. Internal consistency estimates ranged from .62 to .88. Nine of the 10 scales (i.e., all with the exception of the Study Aids) significantly correlated with students' GPAs. Scores obtained from these scales provide valid assessments of Qatar University students' use of learning and study strategies related to skill, will, and self-regulation components of strategic learning and also academic achievement. There also were statistically significant differences between higher and lower achieving students in their learning and study strategies. This study also explored the use of the LASSI as a predictive measure of academic achievement. Anxiety and test strategies were significant predictors of academic achievement as measured by students' GPA.


Optimized clostridium-directed enzyme prodrug therapy improves the antitumor activity of the novel DNA cross-linking agent PR-104.
We have previously shown that spores of the nonpathogenic clostridial strain C. sporogenes genetically engineered to express the E. coli-derived cytosine deaminase gene are effective in converting systemically injected nontoxic 5-fluorocytosine into the toxic anticancer drug 5-fluorouracil, thereby producing tumor-specific antitumor activity. To improve the expression of E. coli-derived genes with this system, we first replaced the original fdP promoter in the vector with one of two powerful endogenous clostridial promoters: that of the thiolase gene (thlP) and that for the clostridial transcription factor abrB310 (abrBP). These substitutions improved protein expression levels of the prodrug-activating genes by 2- to 3-fold in comparison with fdP-driven expression. However, despite these strong promoters, we found much higher expression of the nitroreductase (NTR) protein in the E. coli host compared with the clostridial host, which we hypothesized could be the result of different codon use between the two organisms. To test this, we constructed new expression vectors with an artificially synthesized NTR gene using optimized clostridial codons (sNTR). Results from both enzymatic assays and Western blots of cell extracts from clostridial transformants harboring plasmid constructs of thlP-sNTR and abrBP-sNTR showed that the expression and activity of the NTR gene product was increased by approximately 20-fold compared with the original construct. In vivo studies with i.v. administered sNTR-expressing C. sporogenes spores in SiHa tumor-bearing mice showed significantly improved antitumor efficacy when combined with either 5-aziridinyl-2,4-dinitrobenzamide (CB1954) or the novel dinitrobenzamide mustard prodrug, PR-104.


Synthesis of Three-Dimensional Ring Fused Heterocycles by a Selective [4 + 2] Cycloaddition Between Bicyclic Thiazolo 2-Pyridones and Arynes.
A selective [4 + 2] cycloaddition reaction of thiazolo-2-pyridones with arynes has been demonstrated. The developed protocol allows rapid access to highly functionalized, structurally complex thiazolo-fused bridged isoquinolones in high yields, which are susceptible to further late-stage functionalization.


Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.
Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.


Case reports: two femoral insufficiency fractures after long-term alendronate therapy.
Bisphosphonates are widely used for treatment of postmenopausal osteoporosis. Although short-term safety and efficacy of these drugs have been investigated and documented, an increasing number of recent reports draw attention to the possible correlation between long-term alendronate therapy and the occurrence of insufficiency fractures in the proximal femur owing to what is known as severely suppressed bone turnover. We describe two femoral insufficiency fractures in two women receiving long-term alendronate therapy. The first woman sustained a periprosthetic fracture at the tip of the femoral stem whereas the other woman had a fracture in the subtrochanteric region. We analyze the characteristics and natural course of these two unique fractures, and emphasize the importance of being aware of the possible correlation between long-term alendronate therapy and insufficiency femoral fractures.


Concise intensity statistics of Friedel opposites and classification of the reflections.
A previous extensive analysis of the mean-square intensity difference of Friedel opposites [Shmueli et al. (2008). Acta Cryst. A64, 476-483] is here concisely re-examined and confirmed by purely statistical methods. The analysis applies to noncentrosymmetric crystals only. For special reflections and centered lattices both mean-square intensity difference and average intensity of Friedel opposites depend on the centering factor of the crystal lattice and/or on the isotropy subgroup of the reflection. A complete classification of the reflections, based on the above intensity statistics, is presented. It is also shown that the experimentally important Bijvoet ratio is found to depend only on the chemical composition of the unit-cell content and the wavelength of the radiation.


Ration formulations containing reduced-fat dried distillers grains with solubles and their effect on lactation performance, rumen fermentation, and intestinal flow of microbial nitrogen in Holstein cows.
Sixteen multiparous lactating Holstein cows were used in 2 experiments to evaluate the effects of reduced-fat dried distillers grains with solubles (RFDG) on milk production, rumen fermentation, intestinal microbial N flow, and total-tract nutrient digestibility. In experiment 1, RFDG was fed at 0, 10, 20, or 30% of diet dry matter (DM) to 12 noncannulated Holstein cows (mean ± standard deviation: 89 ± 11 d in milk and 674 ± 68.2 kg of body weight) to determine effects on milk production. In experiment 2, the same diets were fed to 4 ruminally and duodenally cannulated Holstein cows (mean ± standard deviation: 112 ± 41 d in milk; 590 ± 61.14 kg of body weight) to evaluate the effects on rumen fermentation, intestinal flow of microbial N, and total-tract nutrient digestibility. In both experiments, cows were randomly assigned to 4 × 4 Latin squares over 21-d periods. Treatments (DM basis) were (1) control (0% RFDG), (2) 10% RFDG, (3) 20% RFDG, and (4) 30% RFDG. Feed intake and milk yield were recorded daily. In both experiments, milk samples were collected on d 19 to 21 of each period for analysis of milk components. In experiment 2, ruminal pH was measured; samples of rumen fluid, duodenal digesta, and feces were collected on d 18 to 21. Microbial N was estimated by using purines and DNA as microbial markers. Milk yield was not affected by treatment and averaged 34.0 ± 1.29 kg/d and 31.4 ± 2.81 kg/d in experiments 1 and 2, respectively. Percentage of milk protein tended to increase in experiment 1; estimates were 3.08, 3.18, 3.15, and 3.19 ± 0.06% when RFDG increased from 0 to 30% in the diets. However, milk protein concentration was not affected in experiment 2 and averaged 3.02 ± 0.07%. Percentage of milk fat was not affected and averaged 3.66 ± 0.05% and 3.25 ± 0.14% in experiments 1 and 2, respectively. Total ruminal volatile fatty acids and ammonia concentrations were not affected by treatment and averaged 135.18 ± 6.45 mM and 18.66 ± 2.32 mg/dL, respectively. Intestinal microbial N flow was not affected by treatment; however, purines yielded higher estimates of flow compared with DNA markers. When averaged across treatments, intestinal flow of microbial N was 303 and 218 ± 18 g of N/d, using purines and DNA as the markers. Dry matter, organic matter, neutral detergent fiber, and nonfiber carbohydrate digestibility tended to increase with increasing inclusion of RFDG. Results from these experiments indicate that dairy rations can be formulated to include up to 30% RFDG while maintaining lactation performance, volatile fatty acids concentration, and intestinal supply of microbial N.


Characteristics of funding of clinical trials: cross-sectional survey and proposed guidance.
To provide a detailed and current characterisation of funding of a representative sample clinical trials. We also aimed to develop guidance for standardised reporting of funding information. We addressed the extent to which clinical trials published in 2015 in any of the 119 Core Clinical Journals included a statement on the funding source (eg, whether a not-for-profit organisation was supported by a private-for-profit organisation), type of funding, amount and role of funder. We used a stepwise approach to develop a guidance and an instrument for standardised reporting of funding information. Of 200 trials, 178 (89%) included a funding statement, of which 171 (96%) reported being funded. Funding statements in the 171 funded trials indicated the source in 100%, amount in 1% and roles of funders in 50%. The most frequent sources were governmental (58%) and private-for-profit (40%). Of 54 funding statements in which the source was a not-for-profit organisation, we found evidence of undisclosed support of those from private-for-profit organisation(s) in 26 (48%). The most frequently reported roles of funders in the 171 funded trials related to study design (42%) and data analysis, interpretation or management (41%). Of 139 randomised controlled trials (RCTs) addressing pharmacological or surgical interventions, 29 (21%) reported information on the supplier of the medication or device. The proposed guidance addresses both the funding information that RCTs should report and the reporting process. Attached to the guidance is a fillable PDF document for use as an instrument for standardised reporting of funding information. Although the majority of RCTs report funding, there is considerable variability in the reporting of funding source, amount and roles of funders. A standardised approach to reporting of funding information would address these limitations. Future research should explore the implications of funding by not-for-profit organisations that are supported by for-profit organisations.


Adolescent baseball pitching technique: lower extremity biomechanical analysis.
Documentation of the lower extremity motion patterns of adolescent pitchers is an important part of understanding the pitching motion and the implication of lower extremity technique on upper extremity loads, injury and performance. The purpose of this study was to take the initial step in this process by documenting the biomechanics of the lower extremities during the pitching cycle in adolescent pitchers and to compare these findings with the published data for older pitchers. Three-dimensional motion analysis using a comprehensive lower extremity model was used to evaluate the fast ball pitch technique in adolescent pitchers. Thirty-two pitchers with a mean age of 12.4 years (range 10.5-14.7 years) and at least 2 years of experience were included in this study. The pitchers showed a mean of 49 ± 12° of knee flexion of the lead leg at foot contact. They tended to maintain this position through ball release, and then extended their knee during the follow through phase (ball release to maximal internal glenohumeral rotation). The lead leg hip rapidly progressed into adduction and flexion during the arm cocking phase with a range of motion of 40 ± 10° adduction and 30 ± 13° flexion. The lead hip mean peak adduction velocity was 434 ± 83°/s and flexion velocity was 456 ± 156°/s. Simultaneously, the trailing leg hip rapidly extended approaching to a mean peak extension of -8 ± 5° at 39% of the pitch cycle, which is close to passive range of motion constraints. Peak hip abduction of the trailing leg at foot contact was -31 ± 12°, which also approached passive range of motion constraints. Differences and similarities were also noted between the adolescent lower extremity kinematics and adult pitchers; however, a more comprehensive analysis using similar methods is needed for a complete comparison.


Optical switch based on the electrically controlled liquid crystal interface.
The peculiarities of the linearly polarized light beam reflection at the interface within the bulk of a nematic liquid crystal (NLC) cell with different orientations of the director are analyzed. Two methods to create the interface are considered. Combination of the planar and homeotropic orientations of the NLC director is realized by means of a spatially structured electrode under the applied voltage. In-plane patterned azimuthal alignment of the NLC director is created by the patterned rubbing alignment technique. All possible orthogonal orientations of the LC director are considered; the configurations for realization of total internal reflection are determined. The revealed relationship between the propagation of optical beams in a liquid crystal material and polarization of laser radiation has enabled realization of the spatial separation for the orthogonally polarized light beams at the interface between two regions of NLC with different director orientations (domains). Owing to variations in the applied voltage and, hence, in the refractive index gradient, the light beam propagation directions may be controlled electrically.


Integrated care for the frail elderly.
Chronic disease management initiatives have thus far focused on single disease entities. The challenge of an aging population is the occurrence of multiple diseases, complicated by geriatric syndromes, in the same person. The term frailty is used to denote such persons, who are more vulnerable to poor health outcomes when challenged by a health stressor. In this paper, it is argued that frailty is a chronic condition and thus requires a chronic disease management approach. Hospital-based and community interventions for managing frail seniors are discussed, with a focus on enhancing primary care, and with appropriate and targeted support from geriatric specialists in the form of capacity building as well as direct clinical service. Finally, a model for integrating individual geriatric interventions into a broader system is proposed.


The application of cognitive event-related brain potentials (ERPs) in language-impaired individuals: review and case studies.
There is a substantial body of basic research that has utilized ERPs to investigate the neurological basis of cognition. This research has, in turn, led to the development of practical applications of cognitive ERPs in patient populations. In particular, recent work has focused on the development of ERP-based assessment measures for the neuropsychological assessment of dyslexia and language impairments secondary to stroke. This review describes the innovative assessment methods program (IAMP), an initiative to utilize ERPs for a neuropsychological assessment of patients who cannot be evaluated by traditional methods. The success of this program has demonstrated that ERPs can be used to reliably evaluate an individual's reading and speech comprehension abilities, independent of behavioral and speech production impediments. In contrast to traditional neuropsychological assessment, these ERP methods can discern the cognitive strategies used by an individual to perform a task.


A Molecular Pinball Machine of the Plasma Membrane Regulates Plant Growth-A New Paradigm.
Novel molecular pinball machines of the plasma membrane control cytosolic Ca2+ levels that regulate plant metabolism. The essential components involve: 1. an auxin-activated proton pump; 2. arabinogalactan glycoproteins (AGPs); 3. Ca2+ channels; 4. auxin-efflux "PIN" proteins. Typical pinball machines release pinballs that trigger various sound and visual effects. However, in plants, "proton pinballs" eject Ca2+ bound by paired glucuronic acid residues of numerous glycomodules in periplasmic AGP-Ca2+. Freed Ca2+ ions flow down the electrostatic gradient through open Ca2+ channels into the cytosol, thus activating numerous Ca2+-dependent activities. Clearly, cytosolic Ca2+ levels depend on the activity of the proton pump, the state of Ca2+ channels and the size of the periplasmic AGP-Ca2+ capacitor; proton pump activation is a major regulatory focal point tightly controlled by the supply of auxin. Auxin efflux carriers conveniently known as "PIN" proteins (null mutants are pin-shaped) pump auxin from cell to cell. Mechanosensitive Ca2+ channels and their activation by reactive oxygen species (ROS) are yet another factor regulating cytosolic Ca2+. Cell expansion also triggers proton pump/pinball activity by the mechanotransduction of wall stress via Hechtian adhesion, thus forming a Hechtian oscillator that underlies cycles of wall plasticity and oscillatory growth. Finally, the Ca2+ homeostasis of plants depends on cell surface external storage as a source of dynamic Ca2+, unlike the internal ER storage source of animals, where the added regulatory complexities ranging from vitamin D to parathormone contrast with the elegant simplicity of plant life. This paper summarizes a sixty-year Odyssey.


An analysis of the side chain requirement at position 177 within the lactose permease which confers the ability to recognize maltose.
In previous work (Brooker, R. J., and Wilson, T. H. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3959-3963), lactose permease mutants were isolated which possessed an enhanced recognition for maltose. In some of these mutants, the wild-type alanine residue at position 177 was changed to valine or threonine. To gain further insight into the side chain requirement at position 177 that confers maltose recognition, further substitutions of isoleucine, leucine, phenylalanine, proline, and serine have been made via site-directed mutagenesis. Permeases containing alanine or serine exhibited poor maltose recognition whereas those containing isoleucine, leucine, phenylalanine, proline, or valine showed moderate or good recognition. As far as galactosides are concerned, the Val-177, Pro-177, and Ser-177 mutants were able to transport lactose as well as, or slightly better than, the wild-type strain. The other mutants displayed moderately reduced levels of lactose transport. For example, the Phe-177 mutant, which was the most defective, showed a level of downhill transport which was approximately 20% that of the wild-type strain. In uphill transport assays, all of the position 177 mutants were markedly defective in their ability to accumulate beta-D-thiomethylgalactopyranoside against a concentration gradient. Finally, the position 177 mutants were analyzed for their ability to catalyze an H+ leak. Interestingly, even though the wild-type permease does not leak H+ across the bacterial membrane, all of the position 177 mutants were shown to transport H+ in the absence of sugars. For most of the mutants, this H+ leak was blocked by the addition of beta-D-thiodigalactoside. Overall, these results are discussed with regard to the effects of position 177 substitutions on the sugar recognition site and H+ transport.


The squamous cell carcinoma at the level of the cephalic extremity: epidemiological, clinical and histopathological aspects.
Malignant tumors represent one of the most important medical problems, due to the increased mortality rate, life quality alteration, and the lack of a curable treatment. Skin neoplasm ranks first most frequent top primary tumor, summing a higher percentage than any other neoplastic location. It is also known, the fact that, in our country, gastric adenocarcinoma represents the most encountered tumor of the digestive tube. Our case, male, 49-year-old, comes from a rural area, was diagnosed with and surgically treated, within one year, for gastric adenocarcinoma (intestinal type gastric carcinoma) and squamous cell carcinoma (at the level of the lower lip). A high number of etiologic agents are associated with different risks in developing a carcinoma with squamous cells at the level of the head and the neck, and a gastric carcinoma (our patient is known to suffer from gastric ulcer and Helicobacter pylori, for more than 20 years, and he is a chronic consumer of alcohol and nicotine).


Ferromagnetism in annealed Ce0.95Co0.05O2 and Ce0.95Ni0.05O2 nanoparticles.
This paper reports an investigation on the role of transition-metal ions in producing ferromagnetism in CeO2 nanoparticles by electron paramagnetic resonance (EPR). Several samples of CeO2 nanoparticles annealed at 200, 300, 400, and 500 degrees C, doped with 5% Ni and 5% Co ions, characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetry analysis (TGA) and mass spectroscopy (MS), were investigated by X-band EPR at 4, 10 and 300 K, and by magnetometry at 300 K. Magnetic properties and EPR/FMR (Ferromagnetic Resonance) spectra of these nanoparticle samples were found to depend strongly on the annealing temperature (T(A)), oxygen stoichiometry, and dopant-ion species. Different behavior of saturation magnetization in the samples with the dopants, Co and Ni, is found to be due to different-inward and outward-surface diffusion of these impurity ions, respectively, during annealing. A detailed simulation of EPR/FMR spectra of isolated Co and Ni ions carried out here provides in-depth details on the role of the doped ions and oxygen (O-) defects played in the observed magnetic properties.


Association between Dental Caries and Passive Smoking and Its Related Factors in Children Aged 3-9 Years Old.
Dental caries is the most common chronic and infectious childhood disease. Several studies have investigated the side effects of cigarette smoke on oral health. Caries appear to be higher in children exposed to environmental cigarette smoke, but this relationship has not yet been established. The purpose of this study was to investigate the relationship between dental caries and passive smoker children aged 3-9 years old. This descriptive analytical study was performed on 75 children aged from 3 to 9 years. The study included two groups (first group: control, second group: passive smoker). Demographic data, frequency of toothbrushing and using toothpaste, sugar consumption, and number of dental visits were recorded in a questionnaire. Then, the children were examined, and dmft and DMFT index and plaque index were recorded. Children's saliva was then collected and sent to the laboratory for determination of cotinine levels. Then, the relationship between passive smoker and caries index and other factors were statistically analyzed. Studying dmft and DMFT, it was found that except for component M (Missing) which was zero in both groups, the other components of these two indices were significantly higher in the group exposed to passive smoker. Plaque index and salivary cotinine level were also significantly different in the two groups and were lower in the control group. According to the results of this study, children exposed to passive smoker have a higher rate of caries than other children. It seems that it is primarily due to its effect on increasing plaque accumulation and then the effect of passive smoker on the physiological structures of the mouth and so on. We can perform preventive care for children if we know that passive smoking may cause more dental caries. Mosharrafian S, Lohoni S, Mokhtari S. Association between Dental Caries and Passive Smoking and Its Related Factors in Children Aged 3-9 Years Old. Int J Clin Pediatr Dent 2020;13(6):600-605.


Protein kinase A-dependent and -independent signaling pathways contribute to cyclic AMP-stimulated proliferation.
The effects of cyclic AMP (cAMP) on cell proliferation are cell type specific. Although the growth-inhibitory effects of cAMP have been well studied, much less is known regarding how cAMP stimulates proliferation. We report that cAMP stimulates proliferation through both protein kinase A (PKA)-dependent and PKA-independent signaling pathways and that phosphatidylinositol 3-kinase (PI3K) is required for cAMP-stimulated mitogenesis. In cells where cAMP is a mitogen, cAMP-elevating agents stimulate membrane ruffling, Akt phosphorylation, and p70 ribosomal S6 protein kinase (p70s6k) activity. cAMP effects on ruffle formation and Akt were PKA independent but sensitive to wortmannin. In contrast, cAMP-stimulated p70s6k activity was repressed by PKA inhibitors but not by wortmannin or microinjection of the N-terminal SH2 domain of the p85 regulatory subunit of PI3K, indicating that p70s6k and Akt can be regulated independently. Microinjection of highly specific inhibitors of PI3K or Rac1, or treatment with the p70s6k inhibitor rapamycin, impaired cAMP-stimulated DNA synthesis, demonstrating that PKA-dependent and -independent pathways contribute to cAMP-mediated mitogenesis. Direct elevation of PI3K activity through microinjection of an antibody that stimulates PI3K activity or stable expression of membrane-localized p110 was sufficient to confer hormone-independent DNA synthesis when accompanied by elevations in p70s6k activity. These findings indicate that multiple pathways contribute to cAMP-stimulated mitogenesis, only some of which are PKA dependent. Furthermore, they demonstrate that the ability of cAMP to stimulate both p70s6k- and PI3K-dependent pathways is an important facet of cAMP-regulated cell cycle progression.


General motor representations are developed during action-observation.
This study was designed to examine the generality of motor learning by action-observation. During practice, action-observation participants watched a learning model (e.g., physical practice participants) perform a motor sequence-timing task involving mouse/cursor movements on a computer screen; control participants watched a blank screen. Participants transferred to either a congruent (same mouse-cursor gain), or an incongruent (different mouse-cursor gain) condition. As predicted, motor sequence timing was learned through action-observation as well as physical practice. Moreover, transfer of learning to an incongruent set of task demands indicates that the motor representation developed through observation includes generalised visual-motor procedures associated with the use of feedback utilization.


Intracortical connections are not required for oscillatory activity in the visual cortex.
Synchronized oscillatory discharge in the visual cortex has been proposed to underlie the linking of retinotopically disparate features into perceptually coherent objects. These proposals have largely relied on the premise that the oscillations arise from intracortical circuitry. However, strong oscillations within both the retina and the lateral geniculate nucleus (LGN) have been reported recently. To evaluate the possibility that cortical oscillations arise from peripheral pathways, we have developed two plausible models of single cell oscillatory discharge that specifically exclude intracortical networks. In the first model, cortical oscillatory discharge near 50 Hz in frequency arises from the integration of signals from strongly oscillatory cells within the LGN. The model also predicts the incidence of 50-Hz oscillatory cells within the cortex. Oscillatory discharge around 30 Hz is explained in a second model by the presence of intrinsically oscillatory cells within cortical layer 5. Both models generate spike trains whose power spectra and mean firing rates are in close agreement with experimental observations of simple and complex cells. Considered together, the two models can largely account for the nature and incidence of oscillatory discharge in the cat's visual cortex. The validity of these models is consistent with the possibility that oscillations are generated independently of intracortical interactions. Because these models rely on intrinsic stimulus-independent oscillators within the retina and cortex, the results further suggest that oscillatory activity within the cortex is not necessarily associated with the processing of high-order visual information.


Location decision of low-altitude service station for transfer flight based on modified immune algorithm.
The location of Low-Altitude Flight Service Station (LAFSS) is a comprehensive decision work, and it is also a multi-objective optimization problem (MOOP) with constraints. As a swarm intelligence search algorithm for solving constrained MOOP, the Immune Algorithm (IA) retains the excellent characteristics of genetic algorithm. Using some characteristic information or knowledge of the problem selectively and purposefully, the degradation phenomenon in the optimization process can be suppressed and the global optimum can be achieved. However, due to the large range involved in the low-altitude transition flight, the geographical characteristics, economic level and service requirements among the candidate stations in the corridor are quite different, and the operational safety and service efficiency are interrelated and conflict with each other. And all objectives cannot be optimal. Therefore, this article proposes a Modified Immune Algorithm (MIA) with two-layer response to solve the constrained multi-objective location mathematical model of LAFSS. The first layer uses the demand track as the cell membrane positioning pattern recognition service response distance to trigger the innate immunity to achieve the basic requirements of security service coverage. In the second layer, the expansion and upgrading of adjacent candidate sites are compared to the pathogen's effector, and the adaptive immunity is directly or indirectly triggered again through the cloning, mutation and reproduction between candidate sites to realize the multi-objective equilibrium of the scheme. Taking 486,000 km2 of Sichuan Province as an example, MIA for LAFSS is simulated by the MATLAB platform. Based on the Spring open source application framework of Java platform, the cesiumjs map data is called through easyui, and the visualization of site selection scheme is presented with the terrain data of Map World as the background. The experimental results show that, compared with dynamic programming and ordinary immunization, the immune trigger mode of double response and the improved algorithm of operation parameter combination designed by the Taguchi experiment, the total economic cost of location selection is reduced by 26.4%, the service response time is reduced by 25%, the repeat coverage rate is reduced by 29.5% and the effective service area is increased by 17.5%. The security risk, service efficiency and location cost are balanced. The present work is to provide an effective location method for the layout number and location of local transfer flight service stations. For complex scenes with larger scale of low-altitude flight supply and demand and larger terrain changes in the region, the above research methods can be used to effectively split and reduce the dimension.


A novel method to understand tumor cell invasion: integrating extracellular matrix mimicking layers in microfluidic chips by "selective curing".
A major challenge in studying tumor cell invasion into its surrounding tissue is to identify the contribution of individual factors in the tumor microenvironment (TME) to the process. One of the important elements of the TME is the fibrous extracellular matrix (ECM) which is known to influence cancer cell invasion, but exactly how remains unclear. Therefore, there is a need for new models to unravel mechanisms behind the tumor-ECM interaction. In this article, we present a new microfabrication method, called selective curing, to integrate ECM-mimicking layers between two microfluidic channels. This method enables us to study the effect of 3D matrices with controlled architecture, beyond the conventionally used hydrogels, on cancer invasion in a controlled environment. As a proof of principle, we have integrated two electrospun Polycaprolactone (PCL) matrices with different fiber diameters in one chip. We then studied the 3D migration of MDA-MB-231 breast cancer cells into the matrices under the influence of a chemotactic gradient. The results show that neither the invasion distance nor the general cell morphology is affected significantly by the difference in fiber size of these matrices. The cells however do produce longer and more protrusions in the matrix with smaller fiber size. This microfluidic system enables us to study the influence of other factors in the TME on cancer development as well as other biological applications as it provides a controlled compartmentalized environment compatible with cell culturing.


Lewis base sites of non-oxide supports boost oxygen absorption and activation over supported Pt catalysts.
Formaldehyde (HCHO) oxidation to improve indoor air quality has attracted extensive attention. Designing efficient catalysts for HCHO removal at room temperature still remains challenging. Herein, we report a novel strategy to boost HCHO oxidation by the synergistic effect of Pt nanoparticles and C3N4. The pyridine nitrogen of C3N4 can create Lewis base sites, which function in adsorbing and activating O2 molecules. As the preparation temperature increased, the pyridine nitrogen content increased on the C3N4 surface, leading to a more significant synergistic effect. The mechanism study by in situ DRIFTS indicated that the adsorbed O2 molecules were activated by Pt/C3N4. As a result, the Pt/C3N4-650 has the most outstanding performance for HCHO oxidation at room temperature. HCHO can be completely eliminated with a concentration of 80 ppm at room temperature at a GHSV of 50 000 ml g-1 h-1. This study will provide a new perspective to design efficient HCHO oxidation catalysts.


Growth-phase-dependent expression of cspD, encoding a member of the CspA family in Escherichia coli.
The cspD gene of Escherichia coli encodes a protein of high sequence similarity with the cold shock protein CspA, but cspD expression is not induced by cold shock. In this study, we analyzed the regulation of cspD gene expression. By using a cspD-lacZ fusion and primer extension analysis, the expression of cspD was found to be dramatically induced by stationary-phase growth. However, this induction does not depend on the stationary-phase sigma factor sigmaS. Moreover, the expression of cspD is inversely dependent on growth rates and induced upon glucose starvation. Using a (p)ppGpp-depleted strain, we found that (p)ppGpp is one of the positive factors for the regulation of cspD expression.


A pooled analysis of extremely low-frequency magnetic fields and childhood brain tumors.
Pooled analyses may provide etiologic insight about associations between exposure and disease. In contrast to childhood leukemia, no pooled analyses of childhood brain tumors and exposure to extremely low-frequency magnetic fields (ELF-MFs) have been conducted. The authors carried out a pooled analysis based on primary data (1960-2001) from 10 studies of ELF-MF exposure and childhood brain tumors to assess whether the combined results, adjusted for potential confounding, indicated an association. The odds ratios for childhood brain tumors in ELF-MF exposure categories of 0.1-<0.2 μT, 0.2-<0.4 μT, and ≥0.4 μT were 0.95 (95% confidence interval: 0.65, 1.41), 0.70 (95% CI: 0.40, 1.22), and 1.14 (95% CI: 0.61, 2.13), respectively, in comparison with exposure of <0.1 μT. Other analyses employing alternate cutpoints, further adjustment for confounders, exclusion of particular studies, stratification by type of measurement or type of residence, and a nonparametric estimate of the exposure-response relation did not reveal consistent evidence of increased childhood brain tumor risk associated with ELF-MF exposure. These results provide little evidence for an association between ELF-MF exposure and childhood brain tumors.