cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetic consequences of Pleistocene glaciations for the tundra vole (Microtus oeconomus) in Beringia

Repeated glacial events during the Pleistocene fragmented and displaced populations throughout the northern continents. Different models of the effects of these climate-driven events predict distinct phylogeographic and population genetic outcomes for high-latitude faunas. The role of glaciations in (i) promoting intraspecific genetic differentiation and (ii) influencing genetic diversity was tested within a phylogeographic framework using the rodent Microtus oeconomus. The spatial focus for the study was Beringia, which spans eastern Siberia and northwestern North America, and was a continental crossroads and potential high arctic refugium during glaciations. Variation in mitochondrial DNA (cytochrome b and control region; 214 individuals) and nuclear DNA (ALDH1 intron; 63 individuals) was investigated across the Beringian region. Close genetic relationships among populations on either side of the Bering Strait are consistent with a history of periodic land connections between North America and Asia. A genetic discontinuity observed in western Beringia between members of a Central Asian clade and a Beringian clade is geographically congruent with glacial advances and with phylogeographic discontinuities identified in other organisms. Divergent island populations in southern Alaska were probably initially isolated by glacial vicariance, but subsequent differentiation has resulted from insularity. Tests of the genetic effects of postglacial colonization were largely consistent with expansion accompanied by founder effect bottlenecking, which yields reduced diversity in populations from recently deglaciated areas. Evidence that populations in the Beringian clade share a history of expansion from a low-diversity ancestral population suggests that Beringia was colonized by a small founder population from central Asia, which subsequently expanded in isolation.
ELEVATED COPPER REMODELS HEPATIC RNA PROCESSING MACHINERY IN THE MOUSE MODEL OF WILSON'S DISEASE

Copper is essential to mammalian physiology, and its homeostasis is tightly regulated. In humans, genetic defects in copper excretion result in copper overload and Wilson's disease (WD). Previous studies on the mouse model for WD (Atp7b(-)(/-)) revealed copper accumulation in hepatic nuclei and specific changes in mRNA profile prior to the onset of pathology. To find a molecular link between nuclear copper elevation and changes in hepatic transcriptome, we utilized quantitative ionomic and proteomic approaches. X-ray fluorescence and inductively coupled plasma mass spectrometry analysis indicate that copper in the Atp7b(-/-) nucleus, while highly elevated, does not markedly alter nuclear ion content. Widespread protein oxidation is also not observed, although the glutathione reductase SelH is upregulated, likely to maintain redox balance. We further demonstrate that accumulating copper affects the abundance and/or modification of a distinct subset of nuclear proteins. These proteins populate pathways that are most significantly associated with RNA processing. An alteration in splicing pattern was observed for hnRNP A2/B1, itself the RNA shuttling factor and spliceosome component. Analysis of hnRNP A2/B1 mRNA and protein revealed an increased retention of exon 2 and a selective 2-fold upregulation of a corresponding protein splice variant. Mass spectrometry measurements suggest that the nucleocytoplasmic distribution of RNA binding proteins, including hnRNP A2/B1, is altered in the Atp7b(-/-) liver. We conclude that remodeling of the RNA processing machinery is an important component of cell response to elevated copper that may guide pathology development in the early stages of WD.
Prevalence of neural tube defects, folate status, and folate fortification of enriched cereal-grain products in the United States.

In their recent report, Williams et al1 examined data from 21 population-based birth defect surveillance systems for trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups from 1995 to 2002. Data were stratified into pre-, optional, and mandatory fortification intervals, coincident with the authorization of folate fortification of enriched cereal-grain products by the Food and Drug Administration (FDA) in 1996. Williams et al1 found prevalence values per 10000 births for spina bifida for Hispanic, non-Hispanic white, and non-Hispanic black women of 4.18, 3.37, and 2.90, respectively, for the mandatory fortification interval versus corresponding values for the same groups of 6.49, 5.13, and 3.57, respectively, for the prefortification interval. These results suggested that folate fortification was associated with significant decreases in the prevalence of spina bifida among non-Hispanic white and Hispanic births (34% and 36% decreases, respectively). The 19% decline in the prevalence of spina bifida among non-Hispanic black births was borderline statistically significant.1 This failure to find a statistically significant decline among non-Hispanic black births may have been attributable to smaller samples examined (total cases were 515 for non-Hispanic black births, 2672 for non-Hispanic white births, and 1281 for Hispanic births). In their editorial on the article by Williams et al,1 Brent and Oakley2 argued that folic acid fortification levels in the United States are too low. They have inappropriately generalized the data of Williams et al1 into a broad criticism of the current folic acid fortification program and a call for increased fortification. This warrants our response. Consideration of whether increases in fortification are warranted depends a number of complex issues. For example, are the residual neural tube defects (NTDs) in all racial/ethnic groups folate sensitive? If so, then would increasing the levels of folic acid in enriched cereal-grain products … Address correspondence to Jeanne I. Rader, PhD, Division of Research & Applied Technology, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Pkwy, College Park, MD 20740. E-mail: Jeanne.Rader{at}cfsan.fda.gov
Intramolecular acylation of an α-sulfonyl anion generated via halogen-metal exchange of an α-halosulfone bearing an unsymmetrical anhydride

Abstract α-Halosulfones are useful for the in situ preparation of α-sulfonyl anions in the presence of acylating agents bearing enolizable protons. Inter- and intramolecular acylations can be effected by halogen-metal exchange at low temperature.
Heterocyclic and acyclic derivatives of F-N-isopropylacetimidoyl chloride

Abstract F -N-Isopropylacetimidoyl chloride, CF 3 CClNCF(CF 3 ) 2 , has been used as a precursor for a variety of heterocyclic and acyclic compounds. Reaction with azide ion yields a mixture of the imidoyl azide, CF 3 (N 3 )CNCF(CF 3 ) 2 , and the 1,5-tetrazole, CF 3 CNNN CF(CF 3 ) 2 . Hexafluoropropylideniminolithium produces as a minor product the conjugated diimine, (CF 3 ) 2 CNC(CF 3 )NCF(CF 3 ) 2 , from nucleophilic attack at the imidoyl chlorine and as a major product the triimine, (CF 3 ) 2 CNC(CF 3 )NC(CF 3 ) 2 NC(CF 3 ) 2 , from further attack at the isopropyl fluorine. A thio-amide, CF 3 C(S)NHCH(CF 3 ) 2 , and a Δ 3 -1,2,4-dithiazoline, SSC(CF 3 )NC (CF 3 ) 2 , are produced upon reaction of hyrogen sulfide with the imidoyl chloride. Pathways are proposed for each of the reactions.
The Relationship between Osmotic Stress and Calcium Elevation: in vitro and in vivo Rat Lens Models ☆

Abstract Both in vivo and in vitro models were employed in the present study to assess the relative contribution of osmotic stress and increasing calcium levels to the development of sugar cataracts. In galactose cataract obtained from galactosemic weanling rats, the concentration of total calcium increased by nearly 10% at the first sign of visible opacification observed on the fourth day post-galactose feeding. After 7 days of galactose feeding, calcium levels continued to rise, to 0.8 m m . During the first 10 days, loss of lens transparency and calcium elevation was gradual and steady, with precipitous changes occurring on days 11 and 12. In groups of rats where galactose feeding was stopped after 7 days, cataract reversal was followed during the next 5 weeks. During the initial first week of recovery, calcium influx and elevation in the lens continued but began to decline steadily thereafter. After 3 weeks of recovery, lens transparency had returned to almost normal. Calcium levels continued to decline and reached normal levels between day 34 and 42, nearly 4 weeks after removal of the galactose diet. The relationship between osmotic stress and calcium elevation was investigated more directly by culturing normal rat lenses in hypoosmotic medium (280 mOsm) to create osmotic gradients similar to that in galactosemic lenses. The results showed that during the first day of culture (12 hr), osmotically stressed lenses gained 3 mg of water, became opaque and gained excess calcium (7 m m compared to 0.7 m m ). Microscopic vacuoles appeared to accompany the process of opacification and contributed to increased light scattering and the loss of lens transparency. Additional experiments were designed to further distinguish between the effects of osmotic stress and calcium elevation on the opacification process. Thus, lenses were incubated in control and high-calcium medium (20 m m ) at 300 mOsm. Within 12 hr of incubation, calcium elevation progressed to 1.37 m m , nearly doubling the normal value. Although opacification was observed in these lenses, no sign of vacuoles was evident. Collectively, the findings from this study support the premise that an early influx of calcium is brought about by osmotic stress and is responsible for the observed loss in transparency in osmotic (sugar) cataract.
Short- and long-term effects of para-chloroamphetamine on ingestive behavior

Abstract Para-chloroamphetamine (PCA) produces short-term decreases in eating and drinking. PCA also chronically decreases brain serotonin concentration following a single peripheral injection. The present investigation assessed short- and long-term effects of PCA on ingestive behavior and body weight in greater detail. Following an adaptation period, PCA, 0.0, 1.0, 2.0, 5.0 and 10.0 mg/kg, were administered IP, to free feeding rats. A decrease in food and water consumption was observed during the 0–24 hr postinjection period. During the 24–48 hr period, water consumption was significantly increased compared to baseline. Food intakes during this same period returned to baseline levels. No long-term effects on ingestive behavior or body weight were seen during the following 30 days.
Mucous gland basement membrane immunofluorescence in cicatricial pemphigoid.

• Three patients are described with cicatricial pemphigoid and positive immunofluorescence findings in the basement membrane zone of mucous glands of the pharynx, mouth, and nose. These findings appear to be unique to cicatricial pemphigoid. (Arch Dermatol1988;124:1407-1410)
Extended planar defects and the rapid incorporation of Ti 4+ into olivine

The formation of extended planar defects in minerals such as olivine is related to high point defect concentration and can be driven by large gradients in chemical potential, where the energy of the system is lowered by the ordering of defects along specific planes in the crystal. The presence of extended defects has the potential to create the (apparently) anomalous ionic diffusion in olivine as reported recently (Spandler and O’Neill in Contrib Mineral Petrol 159(6):791–818, 2010). High-resolution transmission electron microscopy and energy-filtered imaging were done using experimental samples designed to examine the impact of a TiO2 and f O2 on the potential to form such defects in ferromagnesian olivine. Doped basalt (5 wt% TiO2)–olivine reaction couple experiments were run at 1 atm and 1,310 and 1,410 °C for 50 h at various f O2, ranging from 102 below to 102 above the quartz–fayalite–magnetite buffer. Our results show that extended planar defects in olivine, parallel to {101}ol and occurring in ordered “clusters” with a prolate spheroid geometry ~5–25 nm across and extending up to 150 nm into the olivine, are present near the olivine–glass interfaces in all of our experimental high-TiO2 basalt–olivine samples. Increased Ti content in the olivine is associated with the defects; ordering of Ti4+ and octahedral site vacancies leads to a two- or three-layer superstructure in the olivine. Defect nucleation and growth is driven by the large TiO2 chemical potential gradient across the phase boundary at the start of the experiments, which provides access to microstructures not otherwise present.
Experiments in the Real world

Beck and Eubank (1991) criticize our recent SSLA article (Tomasello & Herron, 1989) on both theoretical and methodological grounds. While we appreciate their attempt to discuss and clarify important issues—and while they do make several sound and very interesting points—in a number of cases they seriously misrepresent our study. We will attempt to address the criticisms in roughly the order in which they were raised.
Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks.

Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29–36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29–36 Hz LFP power. However, mPFC and STN both showed peaks in the 45–55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45–55 Hz activity, the amplitude of the exaggerated 29–36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system.
Safety of Tumour Necrosis Factor-α Antagonists

Tumour necrosis factor-alpha (TNFalpha) is a proinflammatory cytokine that is synthesised by a variety of cell types in response to infectious or inflammatory stimuli. Although TNFalpha plays an adaptive role in immune protection and wound healing at 'physiological' levels, excess TNFalpha production can lead to adverse consequences. TNFalpha is a pivotal cytokine involved in the pathogenesis and progression of rheumatoid arthritis (RA). TNFalpha antagonists have been shown to be effective in the treatment of signs and symptoms of RA and the US FDA has approved three TNFalpha antagonists, etanercept, infliximab, and most recently, adalimumab, for the treatment of RA. However, differences have emerged, with respect to their demonstrated efficacy in other diseases (e.g. Crohn's disease). Worldwide, over half a million patients have been treated with TNFalpha antagonists and concerns regarding their safety have been raised. There is a risk of reactivation of granulomatous diseases, especially tuberculosis, with all three agents and appropriate measures should be taken for detection and treatment of latent infections. An association between non-Hodgkin's lymphoma and treatment with TNFalpha antagonists has been reported, although patients with active, long-standing RA are already known to have an increased incidence of non-Hodgkin's lymphoma. No associations with solid tumours have been found to date. The biological plausibility of lymphomas associated with immunomodulatory agents raises concern and vigilance is appropriate until the relationship is fully characterised. Large phase II and III trials have shown a detrimental effect of TNFalpha antagonists in advanced heart failure and these agents should be avoided in this population. Rare case reports of drug-induced lupus, seizure disorder, pancytopenia and demyelinating diseases have been noted after TNFalpha antagonists and continued vigilance is warranted in patients on TNFalpha antagonists for the development of these diseases. At present there is no evidence implicating TNFalpha antagonists with embryotoxicity, teratogenicity or increased pregnancy loss.
Experimental Studies on the Physiology of the Phycobiont and Mycobiont Ramalina ecklonii By

The lichenized fungus and alga of the fruticose lichen Ramalini ecklonii were isolated into pure cultures. The ascospores of the fungus failed to germinate in less than five weeks incubation in spite of the use of a variety of cultural conditions. The fungus showed a considerable increase in growth on malt extract agar. Both organisms showed a marked tolerance for high concentrations of glucose although growth was quantitatively reduced. The fungus was able to use a variety of carbon and nitrogen sources as well as an extract of algal cells. Cultivation in the absence of biotin and thiamine failed to yield significant amounts of growth. The alga yielded 27 mg of dry weight after three weeks in a synthetic medium under low light intensities. The alga could be grown in satisfactory amounts on CO2 and inorganic salts with moderate light intensities. Experiments using 14CO2 showed the fungus able to incorporate the extra-cellular and intra-cellular products of algal metabolism. The rate of incorporation of extra-cellular products was inhibited by high concentrations of biotin and thiamine. The alga assimilated l4CO2 which was retained by the cells over a period of 14 days, at which time 78 per cent of the activity was insoluble in 80 per cent ethanol. An extract of the fungus labelled with 14C glucose was partially taken up by the alga and 50 per cent of the label was insoluble in 80 per cent after three days incubation in the light. No lichen acids were found in either the fungal cultures or the algal cultures although large amounts (e.g. 2 liters) of material were extracted and chromatographed. Usnic acid was produced by the intact lichen thallus.
Influence of a physical education teacher’s disability on middle school pupils’ learning and perceptions of teacher competence

Limited research has investigated the problems encountered by physical education teachers who have disabilities and instruct able-bodied pupils. The purpose of this study was to examine the influence of a physical education teacher’s disability on middle school pupils’ perceptions of the teacher’s competence and their learning. Participants were 201 7th and 8th grade pupils (age range 12 to 16 years). They were randomly assigned to watch one of two videotaped swimming lessons. These lessons were identical except that in the first lesson the teacher taught from a wheelchair (WCL) while in the second she was able-bodied (ABL). Immediately following the watching of their assigned lesson, pupils completed a questionnaire asking them about their perceptions of the teacher’s competence and an examination over lesson content. Inferential statistical tests revealed that there were no significant differences in the perception and examination scores of those pupils who viewed the WCL and the ABL. These results prov...
The Role of Oxidizing Agent in the Chemistry of In-Situ Uranium Leaching

Synthetic two-component mixtures (uraninite and iron sulfide) as well as native uranium ores obtained from Texas and Wyoming have been examined. Physical/chemical ore properties are correlated with observed laboratory leach response. Data show a large inherent selectivity of oxidant for uranium in the early stages of a leach period. Uranium head grade was found to increase in a nearly linear fashion with hydrogen peroxide concentration in the leach solution. As uranium in the ore is depleted, uranium response decreases and the oxidant serves mainly to leach iron sulfide gangue material. 6 refs.
A connectionist model of conceptual representation

A description is given of a connectionist architecture for modeling conceptual representation. Connectionist structures for capturing property-value bindings, conceptual aspects, scalar properties, property abstraction and inheritance, and category error detection are described. With these structures, the system known as DIFICIL (Direct Inferences and Figurative Interpretation in a Connectonist Implementation of Language comprehension) is able to perform direct inferences, both immediate and mediated, and interpret both literal and figurative adjective-noun combinations. >
Functional role of KLF10 in multiple disease processes

Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Kruppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGFbeta1, 2, 3, E(2), epidermal growth factor, and bone morphogenetic protein-2. TGFbeta inducible early gene-1 activates the TGFbeta-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGFbeta. KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGFbeta inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFbeta.
Effects of the first prepulse on the blink response to a startling noise.

Startle is inhibited when a startling stimulus follows 30―300 ms after a weak prepulse. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is deficient in several neuropsychiatric disorders. Previous reports argue both for and against a learned component to the inhibitory effects of prepulses, but this issue has yet to be fully investigated using stimuli that most commonly detect PPI deficits in clinical populations. If the inhibitory impact of a prepulse is learned, PPI should not be evident when the prepulse is the first stimulus experienced by the subject. Eyeblink electromyography in normal adults was recorded after either a 118 dB(A) 40-ms noise pulse alone (PA) or the same pulse preceded 120 ms by an 86 dB(A) 5-ms noise prepulse (pp + P). In 25 subjects (Order 1), Trial 1 was a PA, and Trial 2 was a pp + P; 23 subjects experienced the opposite order (Order 2). In 34 subjects, Trials 1 and 2 were both PA (control order). Background was 70 dB(A). Startle magnitude increased from Trial 1 to 2 if no prepulse was presented (control order). Compared with the control order, startle inhibition by prepulses was evident in both Orders 1 and 2, and was more robust in Order 2 (first trial = pp + P). Startle magnitude was significantly lower on pp + P than on PA trials in Order 2 but not Order 1 (F < 1). Prepulses inhibit startle on the first pairing with a startling pulse, an effect that cannot be explained by learning.
Hemolytic effect of surface roughness of an impeller in a centrifugal blood pump

The present study investigates how the surface roughness of an impeller affects hemolysis in the pivot bearing supported Gyro C1E3 pump. This study focuses on particular areas of the impeller surface in the impeller type centrifugal pump. Seven Gyro C1E3 pumps were prepared with smooth surface housings and different impeller parts with different surface roughnesses. The vanes, top side, and backside of the impeller were independently subjected to vapor polishing, fine sand blasting, or coarse sand blasting to produce three different grades of surface roughness. These surfaces were then examined by a surface profile instrument. Using these pumps with different impellers, in vitro hemolysis tests were performed simulating cardiopulmonary bypass (5 L/min, 350 mm Hg). The findings of this study conclusively proved that surface roughness of the back side of the impeller has the greatest effect on hemolysis, followed by the top side and then the vanes. The following are reasons for these findings. First, the shear rate may be greater on the back side than on the top side because of the smaller gap between the back and the housing and the greater relative speed against the impeller. Second, the fluid beneath the impeller may have a longer exposure time because there is little chance for the fluid to mix beneath the impeller. Third, the shear rate may be greater on the top side of the impeller than on the vanes because a vortex formation occurs behind the vanes.
Computational modeling of the SiH3+O2 reaction and silane combustion

Abstract Recent theoretical and experimental studies have provided improved estimates of thermochemical and chemical kinetic data for the silicon–hydrogen–oxygen system. In particular, the SiH 3 +O 2 reaction has been the subject of considerable interest. Estimates of rate coefficients for specific SiH 3 +O 2 channels as a function of temperature and of pressure and branching fraction assignments are made in the current work using Quantum Rice–Ramsperger–Kassel (QRRK) analyses for k ( E ) and Master Equation (ME) analyses for fall-off. The QRRK/ME analyses were based on potential energy surface data provided by previous ab initio studies. The overall rate coefficient for SiH 3 +O 2 → products shows a slight negative temperature dependence, which agrees with previous experimental studies. The results indicate significant pressure and temperature dependence for the product branching fractions and are in good agreement with experimental measurements of the SiH 3 +O 2 product channels. In particular, the channel producing H atoms (SiH 3 +O 2 →cyclic-OSiH 2 O+H) is dominant at high temperatures and/or low pressures, and the O-atom channel (SiH 3 +O 2 →H 3 SiO+O) is not significant (>5% branching fraction) below 1000 K at any pressure examined in the QRRK study ( P =0.001–10 atm). A detailed chemical mechanism for silane combustion is presented based on the QRRK estimates and other evaluated rate coefficient and thermochemical parameters. The mechanism is validated at high temperatures by comparison of calculated ignition delay times with shock-tube data and by comparison of calculated OH radical profiles with atmospheric pressure burner data. The mechanism is validated at low temperatures by comparison of ignition times with constant volume explosion data.
Production of Negative Transfer in a Problem-Solving Task:

72 students solved two problems using a source problem designed to inhibit performance on the target problem relative to baseline performance when the target problem was solved alone. Both source and target problems shared surface similarity but were structurally dissimilar. Negative transfer was found for three different source and target combinations. The decreased performance below baseline for three of the source-target programs provides a reliable context to demonstrate negative transfer and facilitate continued investigation of this phenomenon.
Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit.

Objectives We assessed the impact of intravenous fluconazole prophylaxis (FP) in extremely low birth weight (ELBW [ Study design Beginning April 1, 2002, FP was given to ELBW infants aged Results During 2000–2001 and the FP period, the incidence of IC in ELBW infants decreased from 7% (15 of 206) to 2% (5 of 240) (P = .01), and the IC-related mortality rate decreased from 12% (4 of 33) to 0 (0 of 40) (P = .04); the incidence of IC increased from 0.1% (4 of 2806) to 0.2% (8 of 3372) in infants of birth weight ≥ 1000 g (P = .06), and no IC-related deaths occurred. During the FP period, IC developed in older infants (24 vs 12 days; P = .12) who had similar risk factors for IC. Conclusion Invasive candidiasis occurred in our NICU in spite of FP and shifted to bigger, more mature infants who had a better outcome.
Invented Review: Getting Started in Clinical Nutrition Research

Conducting nutrition research projects does not require a large, well-funded laboratory and a team of assistants. The main requirement is an inquisitive, creative, and critical mind face to face with an unsolved problem. Nevertheless, the actual process of getting started in clinical nutrition research can present obstacles for the novice clinician that can impede successful implementation and completion of the project. This article reviews the initial steps involved in generating a hypothesis, study design, and preliminary data analysis.
Abstract 2954: Novel interaction between FLIP/DAPK: role for RON in androgen-independent prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Patients with Hormone refractory metastatic prostate cancer (HRPCA) have a 5-year survival of less than 30%. Therefore, it is imperative that new therapeutic strategies targeting advanced stage prostate cancer (PCA) be developed. 2-Methoxyestradio (2-ME2) is an endogenously produced compound that has been shown to successfully treat PCA. As part of our efforts in understanding its mechanism of action, we discovered that the tyrosine kinase RON (Recepteur ‘Origine Nantais) was a target for inhibition. RON Kinase has been previously shown to be upregulated in murine PCA. RON has also been reported to mediate cell migration, and invasion in various cancers. However, the precise role of RON signaling in prostate carcinogenesis is unclear. Our data revealed that RON is upregulated in HRPCA cell lines and human prostate tumors. Using genetic approaches we found novel, causal association between RON and FLICE-like inhibitory protein, also known as FLIP (a known target of 2-ME2), and an increase in Death Associated Protein Kinase (DAPK1). Interestingly, RON overexpression in early stage PCA cell lines induced the transcriptional activation of the Androgen Receptor (AR) and FLIP. Stimulation of RON with its ligand MSP (macrophage stimulating protein) also yielded heightened promoter activity of AR and its downstream target genes including PSA and FLIP. Functionally, these responses translated to increased cell migration in RON overexpressing cells and loss of this migratory potential with RON silencing. Interestingly, 2-ME2 treatment also reduced the migration of HRPCA cells. Migration in wild-type HRPCA cells is also sensitive to regulation with 2-ME2 treatment. Overall these data suggests that RON kinase is a major player in promoting advanced-stage prostate cancer in part due to its ability to regulate apoptosis through novel FLIP/DAPK1 interaction. Supported by NIH (CA 135451, APK). Citation Format: Izhar S. Batth, Jingjing Gong, A. Pratap Kumar. Novel interaction between FLIP/DAPK: role for RON in androgen-independent prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2954. doi:10.1158/1538-7445.AM2013-2954
FILM ARCHITECTURE IN BIOMOLECULAR ASSEMBLIES. EFFECT OF LINKER ON THE ORIENTATION OF GENETICALLY ENGINEERED SURFACE-BOUND PROTEINS

This contribution presents strategies for the optimization of supramolecular architecture aimed at controlling the organization of biomolecules at solid surfaces. Myoglobin, modified by site-directed mutagenesis to include a unique cysteine residue, is selectively chemisorbed to self-assembled haloalkylsilylated silica surfaces of varying n-alkyl chain length (n = 2, 3, 8, 11, 15) to yield a series of surface-immobilized recombinant protein assemblies. These supramolecular assemblies are probed using tapping mode atomic force microscopy, wettability measurements, Fourier transform infrared spectroscopy, and linear dichroism spectroscopy to determine how the individual components comprising these structures (substrate, silane coupling layer, and protein) influence macromolecular protein ordering and stability. Surface roughness is found to be a minor contributor in the determination of macromolecular ordering in these assemblies. In contrast, the nature of the underlying silane self-assembled coupling laye...
Globally convergent adaptive IIR filters based on fixed pole locations

A new class of adaptive filters, dubbed fixed pole adaptive filters (FPAF's), is introduced. These adaptive filters have infinite impulse responses, yet their adaptation exhibits provable global convergence. Good filter performance with a relatively small number of adapted parameters is permitted by the new filter structure, thus reducing the computational burden needed to implement adaptive filters. The implementation and computational complexity of the FPAF is described, and its modeling capabilities are determined. Excitation conditions on the filter input are established that guarantee global convergence of a standard set of adaptive algorithms. Some methods are described for selecting the fixed pole locations based on a priori information regarding the operating environment of the adaptive filter. The FPAF is tailored to applications by such a procedure, enabling improved performance. In examples, the FPAF is shown to achieve a smaller minimum mean square error, given an equal number of adapted parameters, in comparison with adaptive FIR filters and adaptive filters based on Laguerre and Kautz models.
Promoting Beta-Carotene-Rich Vegetables in an Introductory Nutrition Course: An Intervention

Counseling Education. Sessions included lecture, worksheets, and in-class role-play activities. Outcome Measures and Analysis: Mixed betweenwithin subjects analysis of covariance was conducted to analyze MI knowledge and counseling self-efficacy changes from pre to post within and between groups. Counseling videos were assessed by 2 trained graduate students using the Motivational Interviewing Treatment Integrity (MITI 3.1) instrument. An independent-samples t test was conducted to compare MITI scores of intervention and control groups. Results: After the MI curriculum, the intervention group had significant improvements in MI knowledge from pre to post compared with the control group, but there were no significant improvements in counseling self-efficacy. Four of 5 MITI summary scores were significantly higher in the intervention group compared with the control group. Conclusions and Implications: A short 4-class MI curriculum was sufficient to improve MI knowledge and skills among nutrition undergraduates. Funding: Internal funding.
Polaron Bound in a Coulomb Potential

We have calculated the shift in ground-state energy of an electron bound in a Coulomb potential in a crystal, to second order in the electron-phonon coupling and for arbitrary values of the electron-impurity coupling.
Cardiovascular effects of acupuncture in anesthetized dogs.

Spontaneous sinus arrhythmia (two dogs), pulsus alternans (three dogs), and pulsus alternans followed by sinus arrhythmia (one dog) were corrected by digital pressure or acupuncture at Yang Hsi (LI-5) locus while these animals were under halothane (MAC I) anesthesia. This locus which is used to treat cardiac arrhythmias is located on the medial side of the carpus. EKG, aortic flow, exhausted CO2, aortic pressure and stroke volume were recorded continuously prior to, during, and following digital pressure or acupuncture. Cardiac arrest was produced by exposing two dogs to 1% halothane anesthesia in 6% oxygen, 10% carbon dioxide and 83% nitrogen. The animals recovered from cardiac arrest following acupuncture at the left Jen Ying (St-9) locus and changing from 1% halothane in the hypoxic mixture to 1% halothane in room air. Acupuncture without change from the hypoxic mixture to room air (two dogs) did not result in recovery. The Jen Ying (St-9) locus is found at the bifurcation of the carotid artery. Seven loci, Jen Chung (Go-26), Jen Ying (St-9), Tsu San Li (St-36), Chu Ch'ih (LI-11), Nei Kuan (EH-6), Yung Ch'uan (Ki-1), Yang Hsi (LI-5) were examined for sympathomimetic cardiovascular responses to acupuncture in twelve halothane (MAC I) anesthetized dogs. A good response (+++) was recorded at the Jen Chung (Go-26) locus, a moderate response (++) at the Jen Ying (St-9) locus, poor response (+) at Tsu San Li (St-36), Chu Ch'ih (LI-11) and Yung Ch'uan (Ki-1) loci and no response (-) at the remaining two loci, Nei Kuan (EH-6) and Yang Hsi (LI-5).
Catalytic and receptor-binding properties of the calcium-sensitive phospholipid-dependent protein kinase (protein kinase C) in swine luteal cytosol.

Abstract We have evaluated the catalytic and receptor-binding properties of protein kinase C in swine luteal cytosol using two complementary approaches: (1) assay of catalytic activity assessed as the enzymatic transfer of radiolabeled phosphate to histone III-s acceptor protein in the presence of specific phospholipid, diacylglycerol, or phorbol ester and ionic calcium; and, (2) the high-affinity binding of [ 3 H]phorbol-12, 13-dibutyrate ([ 3 H]PDB) to the protein kinase C receptor. Catalytic properties of pig luteal protein kinase C included: absolute dependence on calcium ions for maximal activation (approximate k a = 0.5 μM); synergistic activation by 1,2-sn-diolein, phospholipid and calcium ions; and rank order of specific phospholipid activational potency: phosphatidylserine > phosphatidic acid > phosphatidylinositol > phosphatidylethanolamine > phosphatidylcholine. The enzyme was also activated by specific phorbol esters at the following half-maximally effective (ED 50 ) concentrations: 12- O -tetradecanoylphorbol-13-acetate (TPA) 11 nM; phorbol-12,13-dibenzoate (PDBe) 26 nM; phorbol-12,13-dibutyrate (PDBu) 33 nM; mezerein 65 nM; and phorbol-12,13-diacetate (PDA) 130 nM. Phorbol-ester receptor properties of protein kinase C included specific, high-affinity ( k d ⋍19 nM), saturable, low-capacity (⋍44 pmol/mg protein) [ 3 H]PDB binding sites. Moreover, the rank order of the equilibrium binding ID 50 s for various phorbol compounds was similar to that of catalytic ED 50 s: viz. 3 nM TPA; 8 nM PDBe; 16 nM PDBu; 19 nM mezerein; and 590 nM PDA. Thus, swine luteal cytosol contains catalytically active protein kinase C with specific phospholipid sensitivity, synergistic activation by diacylglycerol, phospholipid and calcium, and a strict dependence on ionic calcium concentrations that is influenced markedly by the presence of diacylglycerol. In addition, catalytic activity is associated with high-affinity, specific phorbol ester-binding properties that correspond closely to the activational characteristics of this enzyme in this target organ.
Perturbation of thymidine kinase regulation: a novel chemotherapeutic approach.

Abstract The design of compounds which disrupt the regulation of key enzymes is a new strategy for drug development. 5′-AdThd, which can antagonize the feedback inhibition that normally regulates thymidine kinase, is representative of this novel class of agents. The ability of 5′-AdThd to deinhibit thymidine kinase markedly increases the capacity of some cells to phosphorylate thymidine and IdUrd and, thereby, enhance their cytotoxicity. This effect is evident in three human bladder cancer cell lines, but not in normal human urothelial cells. Thus, 5′-AdThd may be able to increase the therapeutic selectivity of IdUrd. Intracellular dTTP pools are critically involved in mediating the effects of 5′-AdThd, but differences in these pools from cell type of cell type may not account for the selective stimulation of IdUrd uptake produced in the cancer cells.
Relationship Status Among Parents of Children with Autism Spectrum Disorders: A Population-Based Study

Despite speculation about an 80% divorce rate among parents of children with an Autism Spectrum Disorder (ASD), very little empirical and no epidemiological research has addressed the issue of separation and divorce among this population. Data for this study was taken from the 2007 National Survey of Children’s Health, a population-based, cross-sectional survey. A total of 77,911 parent interviews were completed on children aged 3–17 years, of which 913 reported an ASD diagnosis. After controlling for relevant covariates, results from multivariate analyses revealed no evidence to suggest that children with ASD are at an increased risk for living in a household not comprised of their two biological or adoptive parents compared to children without ASD in the United States.
Addition of α 1 -Antitrypsin to Surfactant Improves Oxygenation in Surfactant-Deficient Rats. † 1464

During its life cycle, surfactant converts from highly surface active, large aggregates to less surface active, smaller aggregates. This process is probably regulated by a serine protease. We tested whether adding a1-antitrypsin (α1-AT), an antiprotease, to surfactant improves its in vivo function. α1-AT was added to Survanta® and a synthetic surfactant (BC: phospholipids with 3% surfactant peptide B1-78 and 1% palmitoylated surfactant peptide C1-35) at a dose of 100 mg/3 ml surfactant. Adding α1-AT to Survanta and BC did not affect surface activity on a Langmuir/Wilhelmy balance. Adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 ml/kg, and a rate of 60/min. Their lungs were lavaged with saline until the PaO2 dropped below 80 torr, at which time 100 mg/kg of surfactant was instilled. After 60 min of ventilation, the rats were killed and their lungs lavaged. Survanta increased mean arterial/Alveolar PO2 ratios by 91% over post-lavage values versus 136% for Survanta plus α1-AT (p<0.001). BC increased mean arterial/Alveolar PO2 ratios by 173% versus 218% for BC plus α1-AT (p=0.002). Phospholipids in the first and final lavages of rats treated with surfactant without α1-AT were equal, but reduced in the final lavages of rats treated with surfactants plusα1-AT. Total proteins in the final lavages of all groups (1764± 345 μg/ml) were higher (p<0.001) than in the first lavages (211± 59 μg/ml). These data suggest that the addition ofα1-antitrypsin to surfactant has a positive effect on oxygenation in surfactant-deficient rats.
Language learning from texts: mindchanges, limited memory, and monotonicity

Abstract The paper explores language learning in the limit under various constraints on the number of mindchanges, memory, and monotonicity. We define language learning with limited (long term) memory and prove that learning with limited memory is exactly the same as learning via set driven machines (when the order of the input string is not taken into account). Further we show that every language learnable via a set driven machine is learnable via a conservative machine (making only justifiable mindchanges). We get a variety of separation results for learning with bounded number of mindchanges or limited memory under restrictions on monotonicity. A surprising result is that there are families of languages that can be monotonically learned with at most one mindchange, but can neither be weak-monotonically nor conservatively learned. Many separation results have a variant: If a criterion A can be separated from B , then often it is possible to find a family L of languages such that L is A and B learnable, but while it is possible to restrict the number of mindchanges or long term memory on criterion A , this is impossible for B .
Deuterium abundance and background radiation temperature in high-redshift primordial clouds

Measurements of the deuterium abundance in the early Universe provide a sensitive test of the 'standard' Big Bang cosmology. The probable detection of deuterium absorption by a gas cloud between us and a distant quasar suggests an abundance much greater than estimated from observations in the Milky Way, and consistent with the amount of presently observed luminous matter comprising all the baryons in the Universe. The same spectra imply a cosmic background temperature for the early Universe which is consistent with our expectations from standard Big Bang cosmology.
The importance of cellular environment to function of the CD44 matrix receptor

Much has been learned recently by experimental manipulation of the structure of CD44 and assessment of the resulting functions. However, even greater structural variation is naturally introduced by CD44-bearing cells. A structural model is now available for the portion of CD44 that recognizes hyaluronan, but it is clear that all domains of the molecule influence CD44 functions.
High-Energy K -Shell Ionization by Heavy Projectiles

The ionization of $K$-shell electrons by heavy particles is examined in the energy region where the projectile is moving faster than the orbiting electron. An explanation suggested for the rise of the experimental results above the Born approximation is the mechanism of "charge exchange to the continuum." An estimate of the effect shows reasonable agreement with experiment.
Learning from HIV epidemics among injecting drug users

HIV/AIDS was the defining issue for international harm reduction during its first twenty years. This issue was marked by strong contrasts: rapid HIV transmission in some populations of injecting drug users, and close to elimination of HIV in other populations; a formidable research base for designing effective HIV programmes and persistent political problems in implementing evidence-based programmes on a public health scale. Elevated rates of HIV infection among ethnic minority drug users have occurred in many different countries. We do not yet have systematic knowledge of how to reduce stigmatization of AIDS or people who use drugs. Nevertheless, international harm reduction for people who use drugs has moved beyond HIV/AIDS to a variety of other health and social problems, while retaining firm bases in science and human rights.
Morning Cortisol in Relation to Behavioral Symptoms of Nursing Home Residents With Dementia

Behavioral symptoms of dementia (BSD) are a significant challenge for elders, their caregivers, and clinicians, with a prevalence ranging between 66% and 98%. Although several studies have examined BSD type and frequency, few studies have examined a possible neuroendocrine basis of BSD. The purpose of this study was to examine the association between morning cortisol levels and BSD in nursing home (NH) residents. Method: Using a within-subject longitudinal design, saliva was collected four times daily for 5 days to obtain basal cortisol levels from 30 NH residents, aged 80 to 102. Behavior was observed every 20 min for 12 hr/day for 5 days. Mixed-model analysis was used to test the association between morning cortisol (MC) and BSD. To examine the association between MC and BSD across time, participants were divided into low (LM) and high morning (HM) cortisol groups. Results: A significant inverse association between mean overall BSD and morning cortisol (F = 12.71, p = .000) was found. A significant inve...