Unknown Effect Research Articles

PROGRAM AKSI DESA MANDIRI PANGAN DAN KETAHANAN PANGAN RUMAH TANGGA DI KABUPATEN BATANG

Independent Food Village program is a strategic activity to achieve food security of rural region. “Food Village program” activities in Batang were implemented in the Tulis District, Siberuk Village, and in 2008 on the stage of development as well as yet unknown effect on household food security in implementing the program. The Purpose of this study was to analyze the influence of independent village food action programs and the factors affecting food security of the household. Research was conducted with quantitative methods, based on the questionnaire to guide the interview. This study involved 20 respondents, consisting of three affinity groups: productive economic groups, the means of production, and husbandry. The effect of “Food Village program”was analyzed descriptivel;, household food availability is calculated referring to the level of adequacy of food availability for 2200 calories /capita/day, measured in purchasing power of household purchasing power of food sourced from revenue activities “Food Village program” over the last month. Consumption of food was analyzed by looking at the size of food quality; Food distribution was analyzed by knowing the availability of food in quantity by quality, time and quality are right, The degree of household food security was measured two indicators of food security, namely purchasing power and adequacy of energy consumption. Food security action program contributes revenue to the group the means of production of 16.61%, with high purchasing power so that the availability of food in high numbers, quality and safe for consumption so that household food stand in conditions guaranteed. Productive economic groups contributed 13.22% of income, with low food availability and purchasing power in a timely manner as well as safe to eat, so that households have less food. Husbandry groups contributed revenues of 4.28% with low food availability and low purchasing power so that difficulties in obtaining food and causes of household food insecurity conditions.

Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin

Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times. Cancer cell metabolism, characterized by enhanced glucose uptake, production of lactate and anabolism is considered an ideal target for therapeutic interventions. Expression of PKM2 switches metabolism in favor of cancer cells, therefore, the present study was designed to investigate the hitherto unknown effect of resveratrol, a phytoalexin, on PKM2 expression and resultant implications on cancer metabolism. We observed that resveratrol down-regulated PKM2 expression by inhibiting mTOR signaling and suppressed cancer metabolism, adjudged by decreased glucose uptake, lactate production (aerobic glycolysis) and reduced anabolism (macromolecule synthesis) in various cancer cell lines. A contingent decrease in intracellular levels of ribose-5-phosphate (R5P), a critical intermediate of pentose phosphate pathway, accounted for a reduced anabolism. Consequently, the state of suppressed cancer metabolism resulted in decreased cellular proliferation. Interestingly, shRNA-mediated silencing of PKM2 inhibited glucose uptake and lactate production, providing evidence for the critical role of PKM2 and its mediation in the observed effects of resveratrol on cancer metabolism. Further, an over-expression of PKM2 abolished the observed effects of resveratrol, signifying the role of PKM2 downregulation as a critical function of resveratrol. The study reports a novel PKM2-mediated effect of resveratrol on cancer metabolism and provides a new dimension to its therapeutic potential.

Contrast Ultrasound Imaging of the Aorta Alters Vascular Morphology and Circulating von Willebrand Factor in Hypercholesterolemic Rabbits

Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; P(adj) < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.

Zebrafish Chemical Screening Reveals the Impairment of Dopaminergic Neuronal Survival by Cardiac Glycosides

Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA) neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na+/K+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na+/K+ ATPase α3 subunit (ATP1A3). Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

Robust fault tolerant tracking controller design for unknown inputs T–S models with unmeasurable premise variables

This work concerns the tracking problem of uncertain Takagi–Sugeno fuzzy continuous systems with unmeasurable premise variables and affected by unknown inputs. The aim is to synthesize a fault tolerant controller (FTC) ensuring trajectory tracking of a desired reference model. To emit the original plant system, a norm bounded parametric uncertainty is employed in building the T–S model. The control scheme is based on a fuzzy observer to estimate both faults and faulty system states; a proportional integer (PI) observer to estimate constant faults is then adopted. Using descriptor redundancy property and L2 optimization to attenuate the unknown inputs effect, a solution is proposed in terms of bilinear matrix inequalities (BMIs). The performances of the proposed approach are pointed out by accentuating on a model of wastewater treatment plant (WWTP) through numerical results.

Numerical and analytic investigation of a free boundary confluence for the phase field system

In this paper, we demonstrate a new (probably unknown) effect of space-time localized temperature perturbation which occurs in a free boundary confluence in the framework of the phase field model. We numerically approve an analytic formula for the soliton amplitude.

Chromosomal Instability: Mad2 beyond the Spindle Checkpoint

What specific defects can cause chromosomal instability in cancer cells? Overexpression of the mitotic checkpoint protein Mad2 triggers chromosome missegregation but, surprisingly, Mad2 exerts this effect through a previously unknown effect on microtubule dynamics.

Indian Ocean Summer Monsoon (IOSM)-dynamics within the past 4 ka recorded in the sediments of Lake Nam Co, central Tibetan Plateau (China)

In September 2008 several cores (68 cm–115 cm length) (water depth: 93 m) were retrieved from Lake Nam Co (southern-central Tibetan Plateau; 4718 m a.s.l.). This study focuses on the interpretation of high-resolution (partly 0.2 cm) data from three gravity cores and the upper part of a 10.4 m long piston core, i.e., the past 4000 cal BP in terms of lake level changes, hydrological variations in the catchment area and consequently variations in monsoon strength. A wide spectrum of sedimentological, geochemical and mineralogical investigations was carried out. Results are presented for XRF core-scans, grain size distribution, XRD-measurements and SEM-image analyses. These data are complemented by an age-depth model using 210Pb and 137Cs analyses as well as eleven AMS-14C-ages. This model is supported by excellent agreement between secular variations determined on one of the gravity cores to geomagnetic field models. This is a significant improvement of the chronology as most catchments of lacustrine systems on the Tibetan Plateau contain carbonates resulting in an unknown reservoir effect for radiocarbon dates. The good correlation of our record to the geomagnetic field models confirms our age-depth model and indicates only insignificant changes in the reservoir effect throughout the last 4 ka.High (summer-) monsoonal activity, i.e. moist environmental conditions, was detected in our record between approximately 4000 and 1950 cal BP as well as between 1480 and 1200 cal BP. Accordingly, lower monsoon activity prevails in periods between the two intervals and thereafter. This pattern shows a good correlation to the variability of the Indian Ocean Summer Monsoon (IOSM) as recorded in a peat bog ∼1000 km in NE direction from Lake Nam Co. This is the first time that such a supra regional homogenous monsoon activity is shown on the Tibetan Plateau and beyond. Finally our data show a significant lake level rise after the Little Ice Age (LIA) in Lake Nam Co which is suggested to be linked to glacier melting in consequence of rising temperatures occurring on the whole Tibetan Plateau during this time.

Helicobacter pylori induces promoter methylation of E‐cadherin via interleukin‐1β activation of nitric oxide production in gastric cancer cells

Helicobacter pylori infection causes gastric mucosal inflammatory responses, resulting in up-regulation of interleukin-1β (IL-1β) and overproduction of mutagenic nitric oxide (NO). The authors previously demonstrated that IL-1β plays an important role in H. pylori-induced E-cadherin (E-cad) methylation. Here, they extend the study to investigate the downstream effect of IL-1β on H. pylori-induced gastric inflammation and aberrant DNA methylation. Human gastric cancer cell lines (MKN7, MKN74, and TMK-1) with and without pretreatment of IL-1 receptor antagonist (IL-1ra) were treated with IL-1β or infected with H. pylori. Promoter methylation status of E-cad was examined by methylation-specific polymerase chain reaction (PCR). Expression of E-cad, inducible nitric oxide synthase (iNOS), and nuclear factor κB (NFκB) was assessed by quantitative reverse transcriptase PCR, Western blotting, or immunofluorescence. NO production and total DNA methyltransferase (DNMT) activity were assayed fluorometrically. Both IL-1β treatment and H. pylori infection-induced E-cad methylation led to a decrease in E-cad expression at both mRNA and protein levels. Total DNMT enzymatic activity was significantly elevated in treated cells, accounting for the observed E-cad methylation induction. Increased expression of NFκB was accompanied by up-regulation of iNOS and production of NO in treated cells. Reversal of all these phenomena in cells pretreated with IL-1ra suggested H. pylori-induced E-cad methylation via IL-1β stimulation of the NFκB transcriptional system, leading to activation of DNMT activity by NO production. These findings reveal a previously unknown effect of IL-1β and NO on H. pylori-induced aberrant DNA methylation. This possible pathway indicates the role of NO in epigenetic modification that links inflammation to carcinogenesis.

Classification of mismatch repair gene missense variants with PON-MMR

Numerous mismatch repair (MMR) gene variants have been identified in Lynch syndrome and other cancer patients, but knowledge about their pathogenicity is frequently missing. The diagnosis and treatment of patients would benefit from knowing which variants are disease related. Bioinformatic approaches are well suited to the problem and can handle large numbers of cases. Functional effects were revealed based on literature for 168 MMR missense variants. Performance of numerous prediction methods was tested with this dataset. Among the tested tools, only the results of tolerance prediction methods correlated to functional information, however, with poor performance. Therefore, a novel consensus-based predictor was developed. The novel prediction method, pathogenic-or-not mismatch repair (PON-MMR), achieved accuracy of 0.87 and Matthews correlation coefficient of 0.77 on the experimentally verified variants. When applied to 616 MMR cases with unknown effects, 81 missense variants were predicted to be pathogenic and 167 neutral. With PON-MMR, the number of MMR missense variants with unknown effect was reduced by classifying a large number of cases as likely pathogenic or benign. The results can be used, for example, to prioritize cases for experimental studies and assist in the classification of cases.

The Metallurgical Causes of Structural Inhomogeneities in Hot Rolled Bars of Martensitic 12% Chromium Steels

Abstract Signs of segregation found during the goods inwards inspection by the users of hot rolled bars of X20Cr13 turbine blade steel led to difficulties in the customer – supplier relationship, due to their unknown effect on the strength and reliability of the finished component. The aim of this investigation was to characterise the micro structural inhomogeneities metallographically, to discuss the metallurgical causes and possible consequences, and to suggest possible corrective of action.

Quantitative and structural changes of testis and semen quality parameters changes caused by peroral administration of diazinon in rats

The aim of this study was to find the quantitative and structural changes in the rat testis and changes of semen quality after a diazinon administration. METHODS: Rats received diazinon (99% purity) in thier drinking water (40 mg.l-1) with free access. Age of rats at the beginning of the experiment was 30 days and experiment lasted for next 90 days. The histological samples were evaluated by histological and morphometric methods in light microscopy and the samples of semen were evaluated with CASA method. RESULTS: Disintergation of cellular associations in the seminiferous epithelium, germ cells evacuation into the tubule lumen and thier necrosis were mostly observed. Rarely vacuolisation and cracks of epithelium and fibrotisation of interstitial tissue were noted. Morphometric methods have shown extension of epithelium (P&lt;0,01), reduction of tubule lumen (P&lt;0,001) and dilatation of blood vessels (P&lt;0,001). In CASA analysis elevation of all parameters were noted, with statistically significant increase of DSL, VSL, ALH. Dilatation of blood vessels will be probably one of the most significant finding in diazinon toxicity because changes in blood flow in the testis are the key factors of accurate physiological function of testis. The epithelium despite the serious disintegration of germ cells associations and release of these necrotised germ cells to the lumen was significantly extended. This fact indicates the self-reparation compensational function. The same tendency (stimulation effects) has been found in all analysed sperm parameters. It supports previous hypothesis. CONCLUSIONS: Diazinon in this design of experiment causes the disintegration of the germinal epithelium cells associations consequently leading to necrosis and release of these cells to the tubule lumen. Dilatation of blood vessels and unknown stimulation effect on sperm quality parameters are two other common effects of diazinon. We concluded that diazinon in our subchronic low dose test causes middle to moderate histological, morphometric and semen quality changes which were partially compensated with some unknown recovery mechanism. Otherwise, subcellular structures and their functions may be damaged which can lead to subfertility. Further investigation of diazinon is needed for verification of our hypothesis.

Interleukin-12 inhibits the survival of human colon cancer stem cells in vitro and their tumor initiating capacity in mice

Interleukin-12 (IL-12) is a potent immunomodulatory cytokine with unknown direct effect on the property of cancer stem cells (CSCs). In this study, we investigated the capacity of IL-12 to regulate the self-renewal and differentiation of human colon CSCs in vitro, as well as the effect of IL-12 on the growth of tumors initiated by CSCs in mice. After over-expression of IL-12 with lentiviral transfection, CSCs exhibited reduced invasiveness and tumorsphere formation in association with increased apoptosis in vitro. After injection into NOD/SCID mice, tumors initiated by CSCs transfected with IL-12 showed markedly reduced rate of growth. Mechanistic studies revealed that over-expression of IL-12 reduced the expression of IL-4 and STAT6 in CSCs. Thus, our study demonstrates a potentially beneficial role of IL-12 in directly limiting the malignant phenotype of CSCs.

The risks of PPI therapy

PPIs have become one of the most commonly used medications worldwide, as they are the treatment of choice for several acid-related gastrointestinal disorders. However, concerns have been raised about PPI therapy, including the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events. Observational studies have shown very modest associations between PPI therapy and these risks, although the association between PPI treatment and the risk of enteric infections seems to be stronger than the association with other risk factors. However, given the inherent limitations of observational studies, these associations could be attributable to bias and/or confounding factors. In addition, evidence from randomized, controlled trials does not support a clinically significant effect of PPI therapy on the risk of cardiovascular events in patients taking clopidogrel or the risk of pneumonia. Nevertheless, it is impossible to exclude the possibility that some of these associations might be causal or indeed that PPI therapy has an as yet unknown long-term adverse effect. As with any therapy, therefore, it is advisable to prescribe PPIs only to patients for whom these drugs have been proven beneficial.

Novel metabolic aspects related to adenosine deaminase inhibition in a human astrocytoma cell line

Adenosine deaminase, which catalyzes the deamination of adenosine and deoxyadenosine, plays a central role in purine metabolism. Indeed, its deficiency is associated with severe immunodeficiency and abnormalities in the functioning of many organs, including nervous system. We have mimicked an adenosine deaminase-deficient situation by incubating a human astrocytoma cell line in the presence of deoxycoformycin, a strong adenosine deaminase inhibitor, and deoxyadenosine, which accumulates in vivo when the enzyme is deficient, and have monitored the effect of the combination on cell viability, mitochondrial functions, and other metabolic features. Astrocytomas are the most common neoplastic transformations occurring in glial cell types, often characterized by a poor prognosis. Our experimental approach may provide evidence both for the response to a treatment affecting purine metabolism of a tumor reported to be particularly resistant to chemotherapeutic approaches and for the understanding of the molecular basis of neurological manifestations related to errors in purine metabolism. Cells incubated in the presence of the combination, but not those incubated with deoxyadenosine or deoxycoformycin alone, underwent apoptotic death, which appears to proceed through a mitochondrial pathway, since release of cytochrome c has been observed. The inhibition of adenosine deaminase increases both mitochondrial reactive oxygen species level and mitochondrial mass. A surprising effect of the combination is the significant reduction in lactate production, suggestive of a reduced glycolytic capacity, not ascribable to alterations in NAD+/NADH ratio, nor to a consumption of inorganic phosphate. This is a hitherto unknown effect presenting early during the incubation with deoxyadenosine and deoxycoformycin, which precedes their effect on cell viability.

A revised rate‐ and state‐dependent friction law obtained by constraining constitutive and evolution laws separately with laboratory data

We propose two major revisions on the rate‐ and state‐dependent friction (RSF) law on the basis of rigorous analysis of friction experiments. First, we find that the direct effect coefficient a, a parameter playing a central role in the RSF constitutive law, is much larger than the traditional, consensual estimate of less than about 0.01. We derive a lower bound of 0.035 for a directly from stress‐velocity relations measured during carefully designed step tests, without relying on any evolution laws as traditional methods do. After correcting for state changes during the steps, inferred indirectly from observed changes in acoustic transmissivities across the interface, we obtain an estimate of a as large as 0.05. Second, we calculate values of the RSF state variable Φ by feeding the measured shear stress and slip velocity values into the constitutive law. The results showed systematic deviations from predictions of the RSF evolution law of the aging type. This leads us to propose a revised evolution law, which incorporates a previously unknown weakening effect related to the shear stress. We also present additional experiment results to corroborate the presence of this new effect. Forward simulations based on our revised evolution law, combined with the larger, revised value of a, very well explain observed variations in both the shear stress and Φ throughout different phases of experiments, including quasi‐static hold, reloading after a hold, and steady state sliding at different velocities, as well as their mutual transitions, all with an identical set of parameter values.

Experimental evidence of magnetically controlled surface current in hall devices

A previously unknown galvanomagnetic effect in semiconductors (conducting materials) within wide temperature range (77–300K) has been experimentally observed, which is expressed by the appearance of magnetically controlled currents on the opposite lateral boundaries of structures between which Hall voltage is also generated. Surface currents are a linear and odd function of the strength and direction of both the bias current and the magnetic field – if the direction of the magnetic field or the supply current is reversed, the polarity of the surface current will also change. This unexpected surface phenomenon is a direct demonstration of the action of the Lorentz force on the moving charges in semiconductors. The discovered mechanism can enrich the possibilities for surface characterization and rapid determination of the main parameters in solids, such as conductivity type, carrier concentration and carrier mobility. The dependence of the surface current in solids on various nonelectrical quantities is useful for development of new types of sensors for pressure, light, chemical composition etc.

Prediction of Full Field Dynamic Stress/Strain from Limited Sets of Measured Data

Transient events may cause degradation of a structure’s useful life. Often these events have an unknown effect on the structure. Some examples are helicopter hard landing, strong wind gusts on large turbine blades, and other similar occasional events. In many cases, only a handful of sensors are available for the evaluation of these rare, short-term events. This limited data does not always provide the detail necessary in order to determine the effects of the events that occur; this is very important especially in terms of the overall fatigue usage for the system. While a finite element model may be available, use of this limited data does not lend itself to easily integrate into the identification of the dynamic stress and dynamic strain. Often times, estimates of the forcing function can be approximated and used to identify the response. But these techniques are very approximate. A newly developed real time operating data expansion technique has been successfully used for the identification of more detailed information from limited sets of data. This expansion has mainly been used to augment the limited data acquired and allows for better overall visualization of these transient types of events. This technique has mainly been used for general response characteristics for structures. In this work, expansion techniques are developed in conjunction with the finite element mass and stiffness matrices to provide information at all of the finite element degrees of freedom from these limited sets of measured data points. With this approach, dynamic stress and dynamic strain can be identified from measured transient events thereby enabling estimation of fatigue accumulation or usage. Several cases are described to illustrate the overall process and results that are obtained from the expansion technique; these are compared to full reference solution results to verify the accuracy of the technique.

Investigation of blind detection mechanism for chaotic UWB system based on generalized negentrogy

A non-coherent blind detection method based on the generalized negative entropy mechanism for chaotic ultra-wideband system is proposed in this paper. In the case without knowing the transmission channel information, the chaotic impulse signals can be detected. The proposed method can overcome the practical application problem existing in the direct chaotic communication (DCC) scheme for impulse radio ultra-wideband (IR-UWB) communication system. Also, this method can overcome the complicated and unknown multipath channel effect. Analysis of simulation results show that the proposed approach has a good separating and detection performance in the case without the channel information. A new way for the noncoherent blind detection of chaotic UWB system under non-ideal unknown channel is established.

Selenium for preventing cancer

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVE: Two research questions were addressed in this review: What is the evidence for: 1. an aetiological relationship between selenium exposure and cancer risk in women and men?; 2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio, OR, 0.69; 95% confidence interval, CI, 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics. The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification. The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.