Miracle-dz/UniFAR-FTUs huggingface dataset:
CAT2 arginine transporter deficiency significantly reduces iNOS‐mediated NO production in astrocytes

We have previously demonstrated that genetic ablation of cationic amino acid transporter 2 (Cat2) significantly inhibits nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in activated macrophages. Here we report that iNOS activity is impaired by 84% in activated Cat2‐deficient astrocytes. Cat2 ablation appears to reduce astrocyte NO synthesis by decreasing the uptake of the sole precursor, arginine, as well as by reducing the expression of iNOS following activation. Excessive or dysregulated NO production by activated astrocytes and other CNS cell types has been implicated in the pathogenesis of neurological disorders. Our results support the idea that manipulation of CAT2 transporter function might be useful for the therapeutic modulation of iNOS activity.
Monothematic Delusions: Towards a Two-Factor Account

We provide a battery of examples of delusions against which theoretical accounts can be tested. Then we identify neuropsychological anomalies that could produce the unusual experiences that may lead, in turn, to the delusions in our battery. However, we argue against Maher's view that delusions are false beliefs that arise as normal responses to anomalous experiences. We propose, instead, that a second factor is required to account for the transition from unusual experience to delusional belief. The second factor in the etiology of delusions can be described superficially as a loss of the ability to reject a candidate for belief on the grounds of its implausibility and its inconsistency with everything else that the patient knows, but we point out some problems that confront any attempt to say more about the nature of this second factor.
The Conformational Properties of the Highly Selective Cannabinoid Receptor Ligand CP-55,940 (*)

During a search for novel drugs possessing analgesic properties but devoid of the psychotropic effects of marijuana, a group of molecules designated as nonclassical cannabinoids was synthesized by Pfizer. Of these nonclassical cannabinoids CP-55,940 has received the most attention principally because it was used as the high affinity radioligand during the discovery and characterization of the G-protein-coupled cannabinoid receptor. In an effort to obtain information on the stereoelectronic requirements at the cannabinoid receptor active site, we have studied the conformational properties of CP-55,940 using a combination of solution NMR and computer modeling methods. Our data show that for the most energetically favored conformation, (i) the aromatic phenol ring is perpendicular to the cyclohexane ring, and the phenolic O-H bond is coplanar with the aromatic ring and points away from the cyclohexyl ring; ii) the dimethylheptyl chain adopts one of four preferred conformations in all of which the chain is almost perpendicular to the phenol ring; and iii) an intramolecular H-bond between the phenolic and hydroxypropyl groups allows all three hydroxyl groups of CP-55,940 to be oriented toward the upper face of the molecule. Such an orientation by the OH groups may be a characteristic requirement for cannabimimetic activity.
Bacterial pathogens and their antibiotic susceptibility pattern in Intensive Care Units of the University of Maiduguri Teaching Hospital, Nigeria

Background: Nosocomial infections are among leading causes of morbidity and mortality and are associated with increased antibiotic resistance in Intensive Care Units (ICUs). This prospective study was conducted between March and October 2014 in the ICUs of the University of Maiduguri Teaching Hospital to assess the rate, types, and antibiotic susceptibility pattern of airborne and surface-borne bacterial contamination before and after fumigation. Materials and Methods: Sixty samples were collected and investigated from fomites by surface swabbing and open plate air exposure in the ICUs before and after fumigation using standard microbiological methods. Results: Out of the sixty samples investigated, 38 (63.3%) yielded positive bacterial growth. Twenty-six (68%) were before fumigation of the ICU and 31.5% (n = 12) from postfumigation culture. Coagulase-negative Staphylococci spp. (CoNS) accounted for 39.4% (n = 15) of the positive cultures, Bacillus spp. 15% (n = 9), Klebsiella pneumoniae 13.2% (n = 5), Escherichia coli 10.5% (n = 4), Klebsiella oxytoca 7.9% (n = 3), and Streptococcus pyogenes 5.3% (n = 2). The antibiotic susceptibility test results of the isolates revealed that CoNS were resistant to amoxicillin, ampicillin-cloxacillin, and cefuroxime. K. pneumoniae was also resistance to chloramphenicol, aminoglycosides, and penicillins, whereas E. coli showed resistance to fluoroquinolones, particularly pefloxacin and ofloxacin. Conversely, Bacillus spp. , K. oxytoca, and S. pyogenes were susceptibility to all test antibiotics. Conclusion: The high level of bacterial contamination of equipment and inanimate objects in the ICUs and the presence of multidrug resistant bacteria calls for prompt and a holistic infection control interventions.
How does the central nervous system address the kinetic redundancy in the lumbar spine? Three-dimensional isometric exertions with 18 Hill-model-based muscle fascicles at the L4—L5 level

Abstract The human motor system is organized for execution of various motor tasks in a different and flexible manner. The kinetic redundancy in the human musculoskeletal system is a significant property by which the central nervous system achieves many complementary goals. An equilibrium-based biomechanical model of isometric three-dimensional exertions of trunk muscles has been developed. Following the definition and role of the uncontrolled manifold, the kinetic redundancy concept is explored in mathematical terms. The null space of the kinetically redundant system when a certain joint moment and/or stiffness are needed is derived and discussed. The aforementioned concepts have been illustrated, using a three-dimensional three-degrees-of-freedom biomechanical model of the spine with 18 anatomically oriented Hill-type-model muscle fascicles. The considerations of stability and its consequence on the internal loading of the spine and coactivation consequences are discussed in both general and specific cases. The results can shed light on the interaction mechanisms in muscle activation patterns seen in various tasks and exertions and can provide a significant understanding for future research studies and clinical practices related to low-back disorders. Alteration of recruitment patterns in low-back-pain patients has been explained on the basis of this biomechanical analysis. The higher coactivation results in higher internal loading while providing higher joint stiffness that enhances spinal stability, which guards against spinal deformation in the presence of any perturbations.
Physicochemical Properties of Mudskipper (Periophthalmus Barbarus Pallas) Liver Rhodanese.

Cyanide is highly toxic and its ineffective detoxification may result in inhibition of respiration (through iron complexation in cytochrome oxidase), ATP production and other processes dependent on ATP, subcutaneous hemorrhaging, liver necrosis, and hepatic damage in aquatic organisms. Rhodanese a cyanide detoxifying enzyme, was isolated and partially purified from the liver of mudskipper using ammonium sulphate fractionation and Reactive Blue-2 agarose affinity chromatography. The enzyme had a specific activity of 8.4 RU per milligram of protein. The Km values of the substrates (KCN and Na2S2O3) were 33.3 mM and 14.29 mM respectively. The results of substrate inhibition showed that the enzyme was inhibited considerably by sulphide (S 2- ), sulphate (SO 4 2- ) and sulphite (SO 3 2- ) while showing specificity for thiosulphate (S 2 O 3 2- ). The reaction of the enzyme with heavy metals did not show any inhibition. The optimum pH and temperature of the enzyme activity were 8.0 and 50 o C respectively.
Cluster Head Election Mechanism-Based on Fuzzy Logic (Chef) with TDMA in WSN

Abstract Wireless sensor networks (WSN) are being used for huge range of applications where the traditional infrastructure based network is mostly infeasible. The most challenging aspect of WSN is that they are energy resource-constrained and that energy cannot be replenish. the wireless sensor network of power limited sensing devices called sensor deployed in a region to sense various types physical information from the environment, when these sensors sense and transmit data to other sensors present in the network, even the cluster head is elected according to check their residual energy considerable amount of energy will drain automatically to overcome this drawback by considering the protocol a fuzzy logic approach is used to elect the cluster head based on three descriptors-energy, centrality & distance and second CH is elected according to TDMA to overcome the data lost during energy drain occur in the CH . NS-2 simulation shows that proposed protocol provides higher energy efficiency. This paper proposes the mechanism or device is capable of utilizing its own system of control simply called as self-configurable clustering mechanism to detect the disordered CHs and replace them with other nodes. And results have been derived from simulator ns-2 to show the better performance.
Hepatocarcinogenesis following pancreatic islet transplantation in streptozotocin- and autoimmune-diabetic rats

Epidemiological studies assign a role to insulin signalling deregulation and diabetes mellitus in human hepatocarcinogenesis. The underlying mechanisms, however, remain largely unknown. To unravel the molecular pathogenesis of insulin-induced hepatocarcinogenesis, we generated an experimental animal model: after transplantation of only a low number of isologous pancreatic islets into the livers of diabetic rats, mild diabetes persists and the beta cells are maximally stimulated to permanently secrete insulin. As a consequence, liver acini, draining the hyperinsulinemic blood from islet grafts, show insulin-induced adaptive alterations simultaneously resembling preneoplastic foci of chemically-induced hepatocarcinogenesis models. These lesions progress to hepatocellular tumours within 6 and 24 months. Hepatocarcinogenesis is accompanied by alterations in hepatocytes metabolisms and changes in signal transduction pathways that, in the beginning, can be attributed solely to insulin action. In this review, we summarize our findings that may help understanding the oncogenic potential of diabetes mellitus in the human liver.
mTOR-Dependent Regulation of Ribosomal Gene Transcription Requires S6K1 and Is Mediated by Phosphorylation of the Carboxy-Terminal Activation Domain of the Nucleolar Transcription Factor UBF†

ABSTRACT Mammalian target of rapamycin (mTOR) is a key regulator of cell growth acting via two independent targets, ribosomal protein S6 kinase 1 (S6K1) and 4EBP1. While each is known to regulate translational efficiency, the mechanism by which they control cell growth remains unclear. In addition to increased initiation of translation, the accelerated synthesis and accumulation of ribosomes are fundamental for efficient cell growth and proliferation. Using the mTOR inhibitor rapamycin, we show that mTOR is required for the rapid and sustained serum-induced activation of 45S ribosomal gene transcription (rDNA transcription), a major rate-limiting step in ribosome biogenesis and cellular growth. Expression of a constitutively active, rapamycin-insensitive mutant of S6K1 stimulated rDNA transcription in the absence of serum and rescued rapamycin repression of rDNA transcription. Moreover, overexpression of a dominant-negative S6K1 mutant repressed transcription in exponentially growing NIH 3T3 cells. Rapamycin treatment led to a rapid dephosphorylation of the carboxy-terminal activation domain of the rDNA transcription factor, UBF, which significantly reduced its ability to associate with the basal rDNA transcription factor SL-1. Rapamycin-mediated repression of rDNA transcription was rescued by purified recombinant phosphorylated UBF and endogenous UBF from exponentially growing NIH 3T3 cells but not by hypophosphorylated UBF from cells treated with rapamycin or dephosphorylated recombinant UBF. Thus, mTOR plays a critical role in the regulation of ribosome biogenesis via a mechanism that requires S6K1 activation and phosphorylation of UBF.
Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis.

CONTEXT Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. DESIGN Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. RESULTS Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. CONCLUSION Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.
25-Hydroxycholecalciferol(25-OH-D3). 3. Effect of dosage on soft tissue integrity and vitamin D activity of tissue and milk from dairy cows.

Abstract In Trial I, eight cows, two per treatment, were given the following doses of 25-hydroxycholecalciferol: (1) 1.0 mg orally daily for 14 days, (2) 4.0 mg, (3) 8.0 mg, or (4) 16.0 mg intramuscularly in 5 ml sesame oil. No clinical or pathologic evidence of hypervitaminosis D was found. Tissue from animals slaughtered 14 to 35 days after treatment revealed no evidence of tissue irritation and less than a twofold increase in vitamin D content. Tissue from control animals contained 18 to 26 IU of vitamin D per 100 g compared to 20 to 48 IU per 100 g from treated animals. In Trial II, the mean vitamin D content of milk taken on Day 4 postpartum from seven orally-treated cows was not greatly different than that of seven control cows, 35 compared to 31 IU per liter. Similar values for seven intramuscularly injected cows were 75 IU vitamin D per liter compared to 38 for five control cows. Thus, short-term administration of 25-hydroxycholecalciferol at dosages that effectively reduce the incidence of parturient paresis appear safe for the animal, and the products produced by these animals safe for human consumption.
Improved indices of insulin resistance and insulin secretion for use in genetic and population studies of type2 diabetes mellitus

Abstract Homeostasis model assessment (HOMA) provides indices of insulin secretion (β) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P < 0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA′) indices were obtained from β′ = (Ln(FPI)–c)/FPG and R′ = (Ln(FPI)–c)* FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R′), 0.45 (β), 0.39 (β′), all P < 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA- and R were strongly related (r = 0.78, P < 0.0001 vs 0.13) demonstrating substantial misclassification. The relationship between β′ and R′ (r = 0.13) was not different from that between the two direct measures and significant heritability of β′ (h2 = 0.68, P < 0.01) and R′ (h2 = 0.59, P < 0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG. Twin Research (2000) 3, 148–151.
Implementation strategies to enhance management of heavy alcohol consumption in primary health care: a meta-analysis.

BACKGROUND AND AIMS Screening and brief interventions (SBI) delivered in primary health care (PHC) are cost-effective in decreasing alcohol consumption; however, they are underused. This study aims to identify implementation strategies that focus on SBI uptake and measure impact on: (1) heavy drinking and (2) delivery of SBI in PHC. METHODS Meta-analysis was conducted of controlled trials of SBI implementation strategies in PHC to reduce heavy drinking. Key outcomes included alcohol consumption, screening, brief interventions and costs in PHC. Predictor measures concerned single versus multiple strategies, type of strategy, duration and physician-only input versus that including mid-level professionals. Standardized mean differences (SMD) were calculated to indicate the impact of implementation strategies on key outcomes. Effect sizes were aggregated using meta-regression models. RESULTS The 29 included studies were of moderate methodological quality. Strategies had no overall impact on patients' reported alcohol consumption [SMD=0.07; 95% confidence interval (CI)=-0.02 to 0.16], despite improving screening (SMD=0.53; 95% CI=0.28-0.78) and brief intervention delivery (SMD=0.64;95% CI=0.27-1.02). Multi-faceted strategies, i.e. professional and/or organizational and/or patient-orientated strategies, seemed to have strongest effects on patients' alcohol consumption (P<0.05, compared with professional-orientated strategies alone). Regarding SBI delivery, combining professional with patient-orientated implementation strategies had the highest impact (P<0.05). Involving other staff besides physicians was beneficial for screening (P<0.05). CONCLUSIONS To increase delivery of alcohol screening and brief interventions and decrease patients' alcohol consumption, implementation strategies should include a combination of patient-, professional- and organizational-orientated approaches and involve mid-level health professionals as well as physicians.
The Qualitative Similarity Hypothesis

Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within the purview of two groups of cognitive models: those that emphasize the cognitive development of individuals and those that pertain to disciplinary or knowledge structures. It is argued that the QSH has scientific merit with implications for classroom instruction. Future research should examine the validity of the QSH in other disciplines such as mathematics and science and should include perspectives from social as well as cognitive models.
The reliability of the Hendrich Fall Risk Model in a geriatric hospital.

Aims and objectives. The purpose of this study was to test the interrater reliability of the Hendrich Fall Risk Model, an instrument to identify patients in a hospital setting with a high risk of falling. Background. Falls are a serious problem in older patients. Valid and reliable fall risk assessment tools are required to identify high-risk patients and to take adequate preventive measures. Methods. Seventy older patients were independently and simultaneously assessed by six pairs of raters made up of nursing staff members. Consensus estimates were calculated using simple percentage agreement and consistency estimates using Spearman's rho and intra class coefficient. Results. Percentage agreement ranged from 0.70 to 0.92 between the six pairs of raters. Spearman's rho coefficients were between 0.54 and 0.80 and the intra class coefficients were between 0.46 and 0.92. Conclusions. Whereas some pairs of raters obtained considerable interobserver agreement and internal consistency, the others did not. Therefore, it is concluded that the Hendrich Fall Risk Model is not a reliable instrument. The use of more unambiguous operationalized items is preferred. Relevance to clinical practice. In practice, well operationalized fall risk assessment tools are necessary. Observer agreement should always be investigated after introducing a standardized measurement tool.
Endogenous adenosine down-modulates mid-trimester intraamniotic tumor necrosis factor-alpha production.

PROBLEM To determine whether adenosine in amniotic fluid down-regulates pro-inflammatory cytokine production. METHOD OF STUDY Mid-trimester amniotic fluid from 21 women was incubated ex vivo in the presence or absence of human adenosine deaminase, the enzyme that irreversibly degrades adenosine. After 24 hr, supernatants were assayed by ELISA for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10. Clinical parameters were obtained after completion of laboratory testing. RESULTS Inclusion of adenosine deaminase resulted in a median increase in TNF-alpha production from 0.9 to 7.3 pg/mL (P = 0.0014). IL-6 production exhibited a non-significant median increase from <2.0 to 53.0 pg/mL (P = 0.0780). Median IL-10 production increased slightly from a median of <0.2 to 1.3 pg/mL. Adenosine deaminase-stimulated TNF-alpha production was proportional to parity and unrelated to gestational age, time of delivery, maternal age or indication for amniocentesis. CONCLUSION Adenosine deaminase treatment increases TNF-alpha production by ex vivo-cultured amniotic fluid. Adenosine contributes to immune modulation in the amniotic cavity.