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DNA damage induced by reactive oxygen species and several chemotherapeutic agents promotes both p53 and poly (ADP-ribose) polymerase (PARP) activation. p53 activation is well known to regulate apoptotic cell death, whereas robust activation of PARP-1 has been shown to promote a necrotic cell death associated with energetic collapse. Here we identify a novel role for p53 in modulating PARP enzymatic activity to regulate necrotic cell death. In mouse embryonic fibroblasts, human colorectal and human breast cancer cell lines, loss of p53 function promotes resistance to necrotic, PARP-mediated cell death. We therefore demonstrate that p53 can regulate both necrotic and apoptotic cell death, mutations or deletions in this tumor-suppressor protein may be selected by cancer cells to provide not only their resistance to apoptosis but also to necrosis, and explain resistance to chemotherapy and radiation even when it kills via non-apoptotic mechanisms.

A previous contribution in the literature dealt with an interesting way of compensating for the source resistance in the familiar bandpass and bandstop forms of the Wien network in the sense that the centre frequency is maintained at the value for an ideal source. In the present article, the author makes a detailed analysis of these circuits, and shows that in both configurations, not only the centre frequency is maintained constant, but the frequency response can also be improved thereby.

The first Hall network is examined in detail to find and optimize the peak magnitude, which occurs in its bandpass response. It is shown that the same network with a reorientation, can act as a bandstop filter. This is also examined in detail and choice of parameters to maximise the peak/minimize the dip is discussed. In both networks, the critical frequency (of peak/dip) can be controlled by a potentiometer, keeping the magnitude of the peak/dip a constant.

A high-precision parity-violating electron–quark scattering experiment provides measurements of a combination of electron–quark weak couplings with a precision five times higher than the single previous direct study, confirming the predictions of the electroweak particle-physics theory and providing constraints on parity-violating interactions beyond the standard model. Parity-violating asymmetry revisited Parity symmetry — or mirror-image symmetry — implies that flipping left and right does not change the laws of physics. Violation of parity symmetry in the weak nuclear force was discovered in the mid-1950s and parity violation in electron scattering was important in establishing, and is now used to test, the standard model of particle physics. This study reports a high-precision electron–quark scattering experiment that provides a measurement of the parity-violating asymmetry with a precision of five times higher than the single previous direct study via this scattering process. The results confirm the predictions of electroweak particle-physics theory, while providing constraints on parity-violating interactions beyond the standard model. Symmetry permeates nature and is fundamental to all laws of physics. One example is parity (mirror) symmetry, which implies that flipping left and right does not change the laws of physics. Laws for electromagnetism, gravity and the subatomic strong force respect parity symmetry, but the subatomic weak force does not 1 , 2 . Historically, parity violation in electron scattering has been important in establishing (and now testing) the standard model of particle physics. One particular set of quantities accessible through measurements of parity-violating electron scattering are the effective weak couplings C 2 q , sensitive to the quarks’ chirality preference when participating in the weak force, which have been measured directly 3 , 4 only once in the past 40 years. Here we report a measurement of the parity-violating asymmetry in electron–quark scattering, which yields a determination of 2 C 2 u  −  C 2 d (where u and d denote up and down quarks, respectively) with a precision increased by a factor of five relative to the earlier result. These results provide evidence with greater than 95 per cent confidence that the C 2 q couplings are non-zero, as predicted by the electroweak theory. They lead to constraints on new parity-violating interactions beyond the standard model, particularly those due to quark chirality. Whereas contemporary particle physics research is focused on high-energy colliders such as the Large Hadron Collider, our results provide specific chirality information on electroweak theory that is difficult to obtain at high energies. Our measurement is relatively free of ambiguity in its interpretation, and opens the door to even more precise measurements in the future.

Background Community-based programs in rural low-and middle-income country settings are well-placed to conduct gender transformative activities that aid program sustainability and catalyse wider social change, such as reducing gender inequities that in turn improve health outcomes. The Anchal program is a drowning prevention intervention for children aged 1–5 years old in rural Bangladesh. It provides community crèche-based supervision delivered by local trained paid-female volunteers. We aimed to identify the influence of the Anchal program on gender norms and behaviours in the community context, and the effects these had on program delivery and men and women’s outcomes. Methods Qualitative in-depth interviews, focus group discussions and observations were conducted with program beneficiaries and providers. Gender outcomes were analysed using FHI 360’s Gender Integration Framework. Results The Anchal program was found to be a gender accommodating program as it catered for communities’ gender-based roles and constraints but did not actively seek to change underlying beliefs, perceptions and norms that led to these. The program in some cases enhanced the independence and status of female community staff. This changed perceptions of communities towards acceptable levels of physical mobility and community involvement for women. Conversely, gender affected program delivery by reducing the ability of female supervisory staff to engage with male community leaders. The double burden of wage and household labour carried by local female staff also limited performance and progression. Gender-based constraints on staff performance, attrition and community engagement affected efficiency of program delivery and sustainability. Conclusions The Anchal program both adapted to and shaped community gender norms and roles. The program has well-established relationships in the community and can be leveraged to implement gender transformative activities to improve gender-based equity. Health programs can broaden their impacts and target social determinants of health like gender equity to increase program sustainability and promote equitable health outcomes.

Reports on the methylsterol fractions of hazelnut oils are scarce. The objectives of this study were to characterize methylsterols in hazelnut and virgin olive oils and to study the possibility of detection of adulteration of virgin olive oils. In hazelnut oils, 4‐desmethylsterols were present in higher proportions (86 to 91%) than in virgin olive oils where this fraction was ca. 50% of the total sterol. In the 4‐monomethylsterol fraction, citrostadienol was the major component in both kinds of oils followed by cycloeucalenol and obtusifoliol in virgin olive oils, and obtusifoliol in hazelnut oils. 24‐Methylenecycloartanol was predominant in both kinds of oils in the 4,4′‐dimethylsterols. For the first time, δ‐amyrin was tentatively identified by comparing published mass spectral data in the analyzed samples of both kinds of oils. An unknown compound X (containing a lupane skeleton) and lupeol were detected only in the 4,4′‐dimethylsterols fraction of hazelnut oils at a level of 2–8 and 6–10%, respectively. GC‐MS analysis showed that adulteration of virgin olive oil by hazelnut oil could be detected at a level less than 4% by using these two compounds as possible potential markers.

Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D) in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled), and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine) were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato.

Transgenic potato (Solanum tuberosum cv Désirée) plants overexpressing a soybean (Glycine max) type 1 sterol methyltransferase (GmSMT1) cDNA were generated and used to study sterol biosynthesis in relation to the production of toxic glycoalkaloids. Transgenic plants displayed an increased total sterol level in both leaves and tubers, mainly due to increased levels of the 24-ethyl sterols isofucosterol and sitosterol. The higher total sterol level was due to increases in both free and esterified sterols. However, the level of free cholesterol, a nonalkylated sterol, was decreased. Associated with this was a decreased glycoalkaloid level in leaves and tubers, down to 41% and 63% of wild-type levels, respectively. The results show that glycoalkaloid biosynthesis can be down-regulated in transgenic potato plants by reducing the content of free nonalkylated sterols, and they support the view of cholesterol as a precursor in glycoalkaloid biosynthesis.

An extensive aerosol sampling program was conducted during January-December 2006 over Kolkata (22º33′ N and 88º20′ E), a mega-city in eastern India in order to understand the sources, distributions and properties of atmospheric fine mode aerosol (PM 2.5 ). The primary focus of this study is to determine the relative contribution of natural and anthropogenic as well as local and transported components to the total fine mode aerosol loading and their seasonal distributions over the metropolis. The average concentrations of fine mode aerosol was found to be 71.2 ± 25.2 μgm -3 varying between 34.5 μgm -3 in monsoon and 112.6 μgm -3 in winter. The formation pathways of major secondary aerosol components like nitrate and sulphate in different seasons are discussed. A long range transport of dust aerosol from arid and semi-arid regions of western India and beyond was observed during pre-monsoon which significantly enriched the total aerosol concentration. Vehicular emissions, biomass burning and transported dust particles were the major sources of PM 2.5 from local and continental regions whereas sea-salt aerosol was the major source of PM 2.5 from marine source regions.

It is known that the transfer resistance of a resistive ladder can be many times the sum of the actual resistances used to make it. This fact has recently been utilized in constructing ultra-low frequency active-RC filters for biomedical applications, thus saving a significant amount of silicon area in IC implementation. This paper contains an investigation of four kinds of such ladders, viz., (i) L 1 : the R - 2 R ladder, as commonly used in data converters, (ii) L 2 : the R - α R ladder, which is a generalization of L 1 , (iii) L 3 : the arithmetic progression ladder, in which the series resistances as well as the shunt conductances increase from input to output in arithmetic progression, and (iv) L 4 : the geometric progression ladder, in which the series resistances as well as the shunt conductances increase from input to output in geometric progression. While L 1 is analyzed by inspection, L 2 is shown to obey a linear second-order difference equation with constant coefficients, yielding an explicit and elegant expression for the transfer resistance. L 3 and L 4 also obey such a difference equation but not with constant coefficients, and as such, are not amenable to explicit solution. Theses are analyzed here by using the step-by-step ladder analysis method, starting from the output end, and the results for one-, two-, and three-section ladders are given. The four types of ladders are compared on the basis of a specified transfer resistance. It is shown that L 3 and L 4 have several advantages over L 1 and L 2 . However, besides the area saving factor, the choice for a given situation will depend on several factors, viz., the basic resistance, the total resistance used, the number of resistors, the spread of resistors, and the ease of fabricating the resistors, in addition to other possible technological factors.