cssi/SciSciGPT-SciSciNet huggingface dataset:
Quantitation of mitochondrial DNA, RNA, and protein in starved and starved‐refed rat liver

The purpose of this study was to investigate the problem of mitochondrial biogenesis in rat liver. The approach consisted of isolating mitochondria from control, 6 day starved and 6 day starved-5 day refed rats and comparing their DNA, RNA and protein content. This was performed by isolating the mitochondria by reorienting rate zonal centrifugation in sucrose gradients. It was found that six days of starvation resulted in a loss of 30% of the body weight, 55% of the liver weight, 40% of the mitochondrial protein, 60% of the mitochondrial RNA, but only 20% of the mitrochondrial DNA. It was also shown that refeeding of the rats for five days resulted in a restoration to normal or near normal levels in all the parameters measured. Further experiments employing the incorporation of 3H-TTP into into isolated mitochondria indicated that the maintenance of mitochondrial DNA was not the result of continuous DNA sythesis.
Fault Models for Logic Circuits in the Multigate Era

With increased scaling to lower technology nodes, the electrostatic integrity of planar FETs is expected to worsen, necessitating the adoption of low-leakage high-performance multigate FETs, amongst which the FinFET is very attractive with respect to fabrication process complexity. A significant void from a circuit testing viewpoint is the absence of fault models for FinFETs. In particular, it is unclear if CMOS fault models are comprehensive enough to model all defects in FinFET circuits. We investigate the aforementioned problem using mixed-mode FinFET device simulation and demonstrate that while faults defined for planar FETs show significant overlaps with FinFETs, they do not encompass all regimes of operation. Results indicate that no single fault model can adequately capture the leakage-delay behavior of logic gates based on independent-gate FinFETs with opens on the back gate, and shorted-gate FinFETs, which have been accidentally etched into independent-gate structures. To this effect, we categorize back-gate cuts into three regimes where either pulse broadening or pulse shrinking occurs, which can be tested using three-/two-pattern delay fault tests.
Novel 2-Methoxyestradiol Analogues with Antitumor Activity

2-Methoxyestradiol (2-ME2) is a natural estrogen metabolite that, while devoid of estrogenic effects, has both antiangiogenic and antitumor effects. 2-ME2 is currently being evaluated in Phase I and Phase II clinical trials for the treatment of multiple types of cancer. Novel analogues of 2-ME2 were tested for activities that predict antiangiogenic and antitumor effects. Selected analogues were tested for inhibitory activity against endothelial cell proliferation and invasion. The results show that these analogues are effective inhibitors of endothelial cell activities that may predict antiangiogenic activity, and one analogue, 2-methoxy-14-dehydroestradiol (14-dehydro-2-ME2), was 6–15-fold more potent than the parental compound in these assays. The analogues were also evaluated for inhibition of proliferation and cytotoxicity against multiple tumor cell lines and found to be potent and effective. 14-Dehydro-2-ME2 was approximately 15-fold more potent than 2-ME2 against various tumor cell lines, and 2-methoxy-15-dehydroestradiol was particularly effective against DU 145 and PC3 prostate cancer cell lines. In vivo antitumor activity was observed for the three analogues tested in the murine xenograft MDA-MB-435 model; however, 2-ME2 provided no antitumor activity in this trial. The two most effective analogues, 14-dehydro-2-ME2 and 2-methoxyestradiol-15α,16α-acetonide, provided 29.4% and 26.7% inhibition of tumor burden, respectively. Mechanism of action studies indicate that the analogues cause mitotic spindle disruption, mitotic arrest, microtubule depolymerization, and inhibition of the assembly of purified tubulin similar to the effects of 2-ME2. Consistent with antimitotics that inhibit the dynamic instability of tubulin and initiate apoptosis, these novel 2-ME2 analogues cause Bcl-2 phosphorylation and activation of mitogen-activated protein kinase signaling pathways.
Diperoxovanadate alters endothelial cell focal contacts and barrier function: role of tyrosine phosphorylation.

Diperoxovanadate (DPV), a potent tyrosine kinase activator and protein tyrosine phosphatase inhibitor, was utilized to explore bovine pulmonary artery endothelial cell barrier regulation. DPV produ...
PARASITES OF CULTURED EELS1

Glass eel and elver stages of American eel (Anguilla rostrata) collected from Cooper River were stocked separately in ponds at a commercial aquaculture facility near Georgetown, South Carolina, in April 1981. Monthly samples of 15 glass eels and 15 elvers were examined for parasites from May 1981 through July 1982. Cultured glass eels (n=225) harbored 5 species of parasites and cultured elvers (n=225) 11 species. Myxidium giardi was the most frequently encountered parasite in cultured glass eels (43.6%) and elvers (60.4%). The percent occurrence of M. giardi was significantly (P < 0.05) greater in cultured elvers. Occurrence (%) and intensity (parasites/infected eel) of Trichodina sp., the second most frequently encountered parasite, was 10.7% and 3.8 for cultured glass eels and 17.7% and 5.0 for cultured elvers. Occurrence and intensity of Trichodina sp. remained below levels found on wild elvers and elvers treated prophylactically with 100 mg/liter formalin for one hour before stocking ponds. Two species (Henneguya sp. and Ichthyophthirius multifilis) not found in wild eels occurred in cultured elvers and 3 new species (Trichodina sp., Bothriocephalus scorpii, and Philonema sp.) not found in wild glass eels were recovered from cultured glass eels. Management implications in accordance with parasite differences between glass eels and elvers are discussed.
Vibrio cholerae Hemagglutinin/Protease Inactivates CTXφ

Pathogenic strains of Vibrio cholerae are lysogens of the filamentous phage CTXf, which carries the genes for cholera toxin (ctxAB). We found that the titers of infective CTXf in culture supernatants of El Tor CTXf lysogens increased rapidly during exponential growth but dropped to undetectable levels late in stationaryphase growth. When CTXf transducing particles were mixed with stationary-phase culture supernatants of El Tor strains, CTXf infectivity was destroyed. Our data indicate that this growth phase-regulated factor, designated CDF (CTXf-destroying factor), is the secreted hemagglutinin/protease (HA/P) of V. cholerae .A strain containing a disrupted hap gene, which encodes HA/P of V. cholerae, did not produce CDF activity in culture supernatants. Introduction of the HA/P-expressing plasmid pCH2 restored CDF activity. Also, CDF activity in culture supernatants of a variety of pathogenic V. cholerae isolates varied widely but correlated with the levels of secreted HA/P, as measured by immunoblotting with anti-HA/P antibody. CDF was purified from V. cholerae culture supernatants and shown to contain a 45-kDa polypeptide which bound anti-HA/P antibodies and which comigrated with HA/P in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The production of high levels of secreted HA/P by certain V. cholerae strains may be a factor in preventing CTXf reinfection in natural environments and in the human host.
Expression of constitutively active Raf-1 in the mitochondria restores antiapoptotic and leukemogenic potential of a transformation-deficient BCR/ABL mutant

The oncogenic BCR/ABL protein protects hematopoietic cells from apoptosis induced by growth factor deprivation, but the mechanisms are only partially understood. A BCR/ABL mutant lacking amino acids 176-426 in the BCR domain (p185DeltaBCR) failed to protect interleukin 3-deprived 32Dcl3 myeloid precursor cells from apoptosis, although it possessed tyrosine kinase activity and was capable of activating the Ras-Raf-MAP kinase pathway. Compared to p185 wild-type transfectants, p185DeltaBCR-transfected cells showed markedly reduced levels of Bcl-2 and expressed the hypophosphorylated, proapoptotic form of BAD. Bcl-2 expression in the mitochondrial fraction of p185DeltaBCR cells was also markedly diminished and mitochondrial RAF was undetectable. In p185DeltaBCR cells transfected with a mitochondria-targeted, constitutively active RAF (M-Raf) BAD was expressed in the hyperphosphorylated form and released from the mitochondria into the cytosol. p185DeltaBCR/M-Raf-transfected cells were completely resistant to apoptosis induced by growth factor deprivation in vitro. Moreover, constitutive expression of dominant-negative M-Raf (K375W) enhanced the susceptibility of 32Dcl3 cells expressing wild-type BCR/ABL to apoptosis. In severe combined immunodeficiency (SCID) mice, p185DeltaBCR/M-Raf double transfectants were leukemogenic, whereas cells expressing only p185DeltaBCR showed no leukemogenic potential. Together, these data support the existence of a BCR/ABL-dependent pathway that leads to expression of an active RAF in the mitochondria and promotes antiapoptotic and leukemia-inducing effects of BCR/ABL.
Reproductive performance of purebred and crossbred Zebu cattle under artificial insemination in the Amazon tropics

Breeding data from 1543 artificial inseminations, performed on 763 purebred and crossbred zebu cattle reared on 73 small farms, in the Amazon basin of Peru from 1980 to 1986, were evaluated. Inseminations were performed during morning hours using Holstein or Brown Swiss frozen semen. The calving to first oestrus and calving to conception intervals, number of services per conception, intervals between services and conception rate were evaluated. A total of 64-4% of first services and 61-4% of conceptions occurred between the middle of the dry season and the middle of the rainy season. Farm effect proved to be the most important source of variation for all reproductive traits. Other important factors influencing the interval from parturition to first service were breed of cow, parity and season of service. Parity influenced the interval from parturition to conception while parity, time of oestrous detection and inseminator influenced conception rate. The long post-partum anoestrous interval was found to be the most important factor limiting reproductive efficiency on small farms involved in the artificial insemination programme. The reproductive performance of the crossbred cattle tended to be better than that of the purebred zebu cattle.
Insights into Metalloregulation by M-box Riboswitch RNAs via Structural Analysis of Manganese-Bound Complexes.

The M-box riboswitch couples intracellular magnesium levels to expression of bacterial metal transport genes. Structural analyses on other riboswitch RNA classes, which typically respond to a small organic metabolite, have revealed that ligand recognition occurs through a combination of base-stacking, electrostatic, and hydrogen-bonding interactions. In contrast, the M-box RNA triggers a change in gene expression upon association with an undefined population of metals, rather than responding to only a single ligand. Prior biophysical experimentation suggested that divalent ions associate with the M-box RNA to promote a compacted tertiary conformation, resulting in sequestration of a short sequence tract otherwise required for downstream gene expression. Electrostatic shielding from loosely associated metals is undoubtedly an important influence during this metal-mediated compaction pathway. However, it is also likely that a subset of divalent ions specifically occupies cation binding sites and promotes proper positioning of functional groups for tertiary structure stabilization. To better elucidate the role of these metal binding sites, we resolved a manganese-chelated M-box RNA complex to 1.86 A by X-ray crystallography. These data support the presence of at least eight well-ordered cation binding pockets, including several sites that had been predicted by biochemical studies but were not observed in prior structural analysis. Overall, these data support the presence of three metal-binding cores within the M-box RNA that facilitate a network of long-range interactions within the metal-bound, compacted conformation.
Theoretical analysis and modeling of light trapping in a-Si based thin film solar cells

This paper analyses the light trapping effect and finds out that the light path enhancement factor of cells with an ideal Lambertian back reflector (BR) could be as high as n(n+1)2, instead of general quoted 4n2. The program PVOPTICS developed by NREL has been used to modeling the light trapping effect. It is found that 1) the texture angle is more critical than the texture height in determining the light trapping effect, but the latter of which was the only mentioned parameter in general light trapping designs; 2) Inserting a ZnO buffer layer can largely increase the Si absorption, while ZnO thickness does not affect the light trapping obviously, which were confirmed by experimental results; 3) Different impacts of texture starting from a-Si/ZnO or ZnO/metal interface on light trapping effects are studied. For ZnO/Al BR, the texture starting from the a-Si/ZnO interface will lead to a larger absorption in the Si layer; while for ZnO/Ag BR, the texture starting from the a-Si/ZnO interface or ZnO/Ag interface leads to similar results.
Correlation of endocervical curettage with subsequent cone biopsy in the investigation of abnormal cervical cytology

Endocervical curettage and cone biopsy found no high-grade intraepithelial lesions in premenopausal women who had a satisfactory colposcopic evaluation with low-grade cytology and exocervical biopsies. A retrospective analysis was performed of patients who underwent cervical cone biopsy to investigate an abnormal cytology. The histology of the cone was compared with the cervical cytology and the ectocervical biopsies. Over a 6-year period, 346 cone biopsies were performed at the UCLA Medical Center. Of these, 338 cone specimens were available for review, 279 had complete colposcopic records, and 227 had both an endocervical curettage and ectocervical biopsy. No premenopausal patients with low-grade cytology, satisfactory colposcopy and a low grade lesion on ectocervical biopsy subsequently had a high-grade lesion or invasive cancer on the cervical cone biopsy. Thus, in these patients the endocervical curettage did not prove to be of diagnostic value. In contrast, five patients with high-grade cytology, satisfactory colposcopy and low-grade ectocervical lesions had positive endocervical curettages and high-grade lesions on cone biopsy. These data suggest that selective use of endocervical curettage in premenopausal patients with satisfactory colposcopy can be based on whether the cytology is low grade or high grade. In premenopausal patients with low-grade cytology and satisfactory colposcopy, endocervical curettage can be omitted, while any patient who has a high-grade cytology should have an endocervical curettage.
The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine

Galactosamine induces a dose-dependent hepatic injury in rats and many other animals. The toxicity of D-galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D-galactosamine-induced hepatic necrosis in rats. D-Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after D-galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000 subfraction attained statistical significance with respect to the saline control.
Lithium Amidotrihydroborate, a Powerful New Reductant. Transformation of Tertiary Amides to Primary Alcohols.

Abstract Lithium amidotrihydroborate (LiH2NBH3, LAB) is a new and highly nucleophilic reducing agent that is easily prepared by deprotonation of the commerical reagent borane-ammonia complex (H3NBH3) with n-BuLi in tetrahydrofuran (THF) at 0 °C. LAB is found to be a superior reagent for the transformation of tertiary amides into the corresponding primary alcohols.
Design of the DIII-D top level power supply control system for an eighth neutral beam ion source

The DIII-D project will be commissioning an eighth neutral beam ion source during CY09. Part of this effort includes returning one of the neutral beam power supplies (NBPS) to full operation. For the past 10 years, the high voltage DC portion of this system had been used to power gyrotrons in the DIII-D electron cyclotron heating system. The idle filament, magnet, arc and suppressor power supplies will be refurbished using their existing technology. The modulator/regulator for the accelerator (plasma) grid voltage is being upgraded with new controls. Interlocking and coordination of the individual supplies within the NBPS is performed by the local control station (LCS). The new design of the LCS will be presented. The current implementation of the LCS is characterized by discrete relay and CMOS logic and the use of CAMAC interfaces to the neutral beam control and data acquisition systems. These older and difficult to maintain components will be replaced with an Ethernet connected programmable logic controller and a field programmable gate array design for timing functions. Operator interfaces will change from hardwired switches and panels to graphical user interfaces on multiple screens with the capability for remote monitoring and operation. Due to schedule constraints, some of the more reliable solid state circuits in the LCS will not be immediately replaced, but an easy migration path is mapped that will cost minimal downtime once the eighth source is in operation. This project is expected to result in a viable prototype for upgrading each LCS in the other seven neutral beam power systems at DIII-D.
Polymorphism screening of PIK4CA: possible candidate gene for chromosome 22q11-linked psychiatric disorders.

Lithium is potent non-competitive inhibitor of an enzyme involved in the metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P(2)), a critical phosphoinositide (PI) that regulates signal transduction and synaptic vesicle function. Interestingly, a number of genes involved in the regulation of PtdIns-4,5-P(2) synthesis and dephosphorylation are found in regions of the genome previously mapped in bipolar disorder (BPD) including 10p, 18q, 21q, and 22q. One is PIK4CA, a member of the phosphatidylinositol 4-kinase family that phosphorylates PtdIns at the D4 position of the inositol ring as part of the PtdIns-4,5-P(2) synthetic pathway. PIK4CA maps to 22q11 in a region believed to contain a susceptibility gene for psychiatric disorders. Screening of two functional domains of PIK4CA and the promoter region resulted in the identification of 15 different polymorphisms. Rare variants at a consensus splice donor site and the promoter region were found in a total of three patients with BPD, three with schizophrenia (SZ) and only one control. Several common non-synonymous changes and a common single nucleotide polymorphism (SNP) at position -31 in the putative promoter were identified and analyzed in patients with BPD, SZ, and controls. There was no difference in the allele distribution in mentally ill subjects and controls for two variants, R2259C and E2079Q, both located in the PIK4CA catalytic domain. There was, however, a trend toward significance in the distribution of the -31 promoter genotypes in bipolar subjects and controls. Although the results of this analysis were modest, considering the heterogeneity of BPD and SZ and the hypothesis that BPD may be caused by abnormalities in genes that regulate PI-mediated phenomena in the brain, the polymorphisms we detected in the PIK4CA gene should be analyzed in a larger data set to help determine their significance in 22q11-linked mental disorders.
Abandoning Their Mission

This brief essay explores Christopher Newfield's strong claims that the successful culture wars of the political right have "severed the public university from its broader base" and "led to [their] abandonment of egalitarian and democratic impulses". I offer my own experiences as president of the College of William & Mary as partial ratification of Newfield's arguments. But, ultimately, I conclude that Newfield overstates the impact of the culture warriors. We are witnessing, I claim, a dramatic abandonment of the public mission of our strongest public universities; an abandonment that betrays the central purposes of public higher education. The causes, though, lie considerably closer to home.
Two cheers for Bayes's theorem

In Particles and Waves [1], Peter Achinstein offers a formal proof that the incremental concept of confirmation associated with Bayes's theorem is not unrestrictedly true. Contrary to popular belief, Achinstein argues, it is not the case that successful prediction (or retrodiction) of observable phenomena always increases the probability of a hypothesis. Achinstein offers to counterexample the incremental concept by specifying conditions under which it would generate a contradiction. If his argument were correct, it would have far-reaching consequences for the philosophy of science. In particular, it would lend considerable support to the view advanced by Laudan [2] that information regarding rivals is always critical to the question of confirmation. But although his argument is valid, it is unsound: the contradiction arises not through any fault in Bayes's theorem but because of an inconsistency in Achinstein's initial conditions.
Curvilinear allometry, energetics and foraging ecology: a comparison of leaf-cutting ants and army ants

Allometric scaling in ants with polymorphic castes often remains curvilinear after logarithmic transformation. A technique for comparing non-linear scaling is developed and used to compare caste polymorphism in the leaf-cutting ant Atta colombica Guerin and the army ant Eciton hamatum (Fab.). Of the five morphological characters compared, the scaling of leg length to the cube root of body mass (M1l3) differed the most: relative leg length increased with M1l3 in E. hamatum and decreased with M1l3 in A. colombica. This difference reflected species differences in the energetics and foraging behaviour. Key-words: Atta colombica, Eciton hamatum, leafcutters, army ants, curvilinear allometry, foraging ecology
Theoretical study of negative optical mode splitting in LaAl O 3

We analyze the general circumstances that can lead to the negative longitudinal/transverse optical mode splitting (the Lyddane-Sachs-Teller splitting). As a specific example, we consider the optical phonon frequencies of perovskite $\mathrm{LaAl}{\mathrm{O}}_{3}$ computed within density functional theory and compare them to prior experimental reports. The experimental results and theoretical calculation convincingly show that one of the optical mode splittings is indeed negative. The specific optical mode in experiment experiencing the negative splitting is consistent with our analysis. As a typical negative splitting is rather small and close to the experimental resolution, our analysis provides a firm theoretical basis for its existence.
Prenatal Nicotine Exposure Augments Renal Oxidative Stress in Embryos of Pregnant Rats with Reduced Uterine Perfusion Pressure

Background/aim Both maternal nicotine (NIC) exposure and placental insufficiency increase oxidative stress in the fetal kidney ensuing fetal programming of renal diseases in adult life. Their combined effects, however, are unknown. We tested the hypothesis that maternal NIC exposure exacerbates renal oxidative stress and injury in fetuses of pregnant rats with placental insufficiency. Materials and methods Fourteen-day-pregnant rats were subjected to sham operation or reduced uterine perfusion pressure (RUPP) that received either nicotine (20 μg/ml in 1% saccharine) or vehicle (1% saccharine) in their drinking water. At gestational age of 21 days, male fetuses were collected by C-section and sacrificed: plasma and renal cotinine content, extent of renal oxidative stress (4-hydroxynonenal [HNE] and HO-1) and injury (KIM-1) were determined together with the weight of the fetal kidney and fetus. Results Prenatal NIC exposure resulted in cotinine accumulation in the plasma and kidney of the fetuses, augmented RUPP-associated increase in renal HNE content and HO-1 expression as well as KIM-1 expression. NIC also enhanced RUPP-induced reduction in fetal and fetal kidney weight. Conclusion Prenatal NIC exposure augments the existing renal risk in the growth-restricted fetus, which may contribute to worsening in fetal programming of renal disease.
Quantitative methods to determine efficacy of treatment in achalasia

Determining success after achalasia therapy is an important aspect of treating this disease. Esophageal manometry, scintigraphy, and barium esophagram are the most commonly employed techniques. Recent data suggest that barium esophagram may be most practical and informative compared to manometry and scintigraphy in predicting treatment success in achalasia patients after therapy.
The Restoration chapter in the history of English law reform

This article attempts to show that both the Restoration era law reform efforts (1660-1688) were part of a long term tradition. It examines reforming efforts that began as least as early as the reign of Henry VIII and extended well into the eighteenth century. Whether or not law reform proposals became law, and most did not, early modern English parliaments were at the center of law reform efforts. It emphasizes the continuity of complaints, the similar nature of reform bills offered and the difficulty of transforming them into statutes. It argues that the desire for and the inability to achieve law reform was a characteristic of the entire early modern period, rather than a lamentable failure of the revolutionary era.
Antibody Microarrays: Analysis of Cystic Fibrosis

Cystic fibrosis (CF) is the most common autosomal recessive disease in the USA and Europe, whose life-limiting phenotype is manifest on epithelial cells throughout the body. The principal cause of morbidity and mortality is a massively proinflammatory condition in the lung. The mutation responsible for most cases of CF is [ΔF508]CFTR. However, the penetrance of the disease is quite variable, and adverse events leading to hospitalization cannot be easily predicted. Thus, there is a strong need for prognostic endpoints that might serve to identify impending clinical problems long before they happen. Our approach has been to search for proteomic signatures in easily accessed biological fluids that might identify the molecular basis for adverse events. We describe here a workflow that begins with patient-derived bronchial brush biopsies and progresses to analysis of serum and plasma from patients on antibody microarrays.
Bortezomib in Combination with Dexamethasone and Pegylated Liposomal Doxorubicin (DoVeD) Breaks Plateau Responses Following Initial Induction Therapy in Multiple Myeloma: Results of a Phase II Pilot Study.

Abstract 2311 Poster Board II-288 Improved quality of response to induction therapy has been shown to be associated with improved long-term outcomes, including prolonged progression-free (PFS), event-free, and overall survival (OS), in newly diagnosed multiple myeloma (MM) patients (pts). Induction regimens incorporating the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have demonstrated high overall response rates (ORR), and substantial complete response (CR) and very good partial response (VGPR) rates in MM; however, while a large majority of pts respond, a proportion does not achieve ≥VGPR. Per the Norton–Simon hypothesis, the sequential, dose dense, use of agents or regimens that are not cross-resistant may improve the proportion of pts achieving CR or VGPR to induction therapy, and subsequently improve long-term outcomes. This phase II pilot study investigated the efficacy and safety of bortezomib + dexamethasone ± liposomal doxorubicin (DoVeD) in MM pts who had reached a response plateau ( Disclosures: Mark:Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Zafar:Celgene Corp: Speakers Bureau; Millenium: Speakers Bureau. Crann:Milllennium: Membership on an entity9s Board of Directors or advisory committees. Leonard:Milllennium: Consultancy; Johnson & Johnson: Consultancy. Coleman:Celgene Corp: Speakers Bureau; Millenium: Speakers Bureau; Immunomedics: Membership on an entity9s Board of Directors or advisory committees. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding, Speakers Bureau; Proteolix: Consultancy, Research Funding.
Statistical comparison of likelihood models for low dose x-ray CT

Iterative reconstruction in x-ray CT using maximum likelihood estimation (MLE) seeks to improve image quality over analytic techniques by accurately modeling the statistics of the CT acquisition. However there are a variety of statistical models to choose from, each providing a different tradeoff between data fidelity and computational simplicity. In this work, we simplify the reconstruction task to estimating the depth of a single stack of material, which makes estimation tractable for any model. We use this methodology to compare the tradeoffs of different statistical models. We specifically focus on comparing the added value in using complex, clinically infeasible models over conventional ones. The likelihood function for various statistical CT models is calculated either analytically or computationally for a particular x-ray source/detector system. Computational likelihoods are built through repeated calculation of their density functions. From these likelihoods, the bias and variance of each MLE are calculated. Excluding electronic noise, the bias and variance improvements of accurately modeling quantum noise with a compound Poisson model are negligible after accounting for beam hardening. Two strategies for including electronic noise - as additive Gaussian noise in the likelihood vs simple thresholding - are examined. Although each strategy leads to different estimates at low signals, their overall performance is similar. While accounting for beam-hardening of multi-energetic x-ray spectrum is important, we found that the benefit of modeling energy-integrating detectors is negligible. Also, while the presence of electronic noise worsens estimation performance at low signal levels, incorporating electronic noise in the likelihood model doesn't improve performance compared to thresholding.
Thinking outside anthropology's box: Socializing undergraduates through collaborative research, teaching, and service

Most undergraduate anthropology majors will not pursue postgraduate careers in the discipline, so the greatest value of anthropological training is in providing a holistic sense of cultural relativity and appreciation for human diversity. However, translating anthropology's value to other career paths is frequently hindered by students’ limited exposure to theory and methods and further complicated by the discipline's emphasis on individualistic fieldwork models and research outcomes. We argue these obstacles can be overcome by engaging students in mixed-methods collaborative groups that integrate students and faculty in local research, teaching, and outreach. This socializes undergraduates to view anthropology as naturally collaborative and applicable beyond careers in research. In this article, we outline a program that fuses experimental and field approaches to train students in qualitative and quantitative methods and critical thinking. We then detail implementation of this pedagogical model as a generalizable template that trains students for postgraduate careers outside anthropology.
HCV and HIV Envelope Proteins Co-Operatively Induce Fas-Mediated Apoptosis Via a Novel Stat1 Signaling Pathway.

Abstract Hepatitis C virus (HCV) co-infects approximately 40% of patients with human immunodeficiency virus (HIV). HCV/HIV co-infected patients often have progressive liver disease that can lead to cirrhosis and death. We observed that hepatocytes exposed to HCV and HIV envelope proteins undergo apoptosis via an ‘innocent bystander' mechanism due to cell surface binding of viral proteins independent of direct viral infection. HCV envelope protein E2 (1.5 nM) and HIV envelope protein gp120 (0.8 nM) derived from M-tropic and T-tropic viruses induce significant apoptosis in both hepatocytic cell lines and primary hepatocytes, while either of these viral proteins alone does not. Now, we have elucidated the signaling mechanisms that mediate this effect. HCV-E2 and HIV-gp120 were found to significantly upregulate Fas ligand (FasL). We then examined the Stat family of proteins known to participate in FasL and apoptotic pathways. We observed an increased DNA binding activity of Stat1 upon HCV-E2 and HIV-gp120 stimulation. Furthermore, overexpression of wild type Stat1αincreased apoptosis and FasL expression in HepG2 cells, whereas a C-terminal domain deleted mutant, Stat1β, decreased HCV-E2 and HIV-gp120 mediated apoptosis and FasL upregulation. Overexpression of Stat1αand Stat1β in primary hepatocytes confirmed that Stat1αenhanced apoptosis upon HCV-E2 and HIV-gp120 treatment. We observed a tyrosine dependent activation of Stat1 and a subsequent serine phosphorylation of Stat1. TYK2, lyn kinase, RAFTK and MAP kinases were activated upstream of Stat1. In addition, Stat1 associated with the death domain-containing adapter protein TRADD. TRADD is known to induce inflammatory signaling through the NFκB pathway. Here, the association of Stat1 with TRADD would reduce the availability of TRADD to induce NFκB. Thus, Stat1 sequestration of downstream apoptotic signaling molecules would block the host inflammatory response. Further characterization of Fas-mediated apoptosis revealed that caspase 3 and caspase 7 were activated following HCV-E2 and HIV-gp120 stimulation. However, we were not able to detect significant activity of either caspase 8 or caspase 9. We also found a loss in mitochondrial membrane potential upon HCV-E2 and HIV-gp120 stimulation, which leads to the release of cytochrome C and AIF into the cytosol. Taken together, these studies indicate that the viral proteins of HCV and HIV co-operate in causing the apoptosis of hepatocytes, independent of direct infection, by induction of novel Stat1 downstream signaling pathways at the expense of a normal host inflammatory response.
Sideshows at the Center - British Campaigns in the Middle East during the Great War

This article places the Middle East campaigns at the heart of the effort to understand the First World War's cultural impact in Britain. By doing so, it shows that the effects typically attributed to the western front—loss of faith in technology and heroism—were mediated in important ways by lessons emerging from the Middle Eastern fronts in Palestine and Mesopotamia, where the British found their faith in technology strengthened. By incorporating that cultural legacy, we can better understand why Britons remained committed to the war and why they maintained their faith in industrial development and imperial warfare after the war had ended. The heroic image of T. E. Lawrence and of the infrastructural development undertaken by the British military in Mesopotamia bolstered faith in technology and imperialism just when the western front was revealing their darker side. The article begins with a study of the unique military tactics the British adopted in the region, shaped by particular cultural notions about a largely imaginary “Arabia”: deception, irregular warfare, and airpower were used to an unprecedented degree in these campaigns. It goes on to show how the British government strove to capitalize on the propaganda effects of these “sideshows” as they became successful. In particular, they stressed the notion that the empire could find redemption in the restoration of the ancient “cradle of civilization.” Such ideas sustained idealistic notions even as the western front unleashed a new kind of cynicism.
Molecular mechanism of reflectin’s tunable biophotonic control: Opportunities and limitations for new optoelectronics

Discovery that reflectin proteins fill the dynamically tunable Bragg lamellae in the reflective skin cells of certain squids has prompted efforts to design new reflectin-inspired systems for dynamic photonics. But new insights into the actual role and mechanism of action of the reflectins constrain and better define the opportunities and limitations for rationally designing optical systems with reflectin-based components. We and our colleagues have discovered that the reflectins function as a signal-controlled molecular machine, regulating an osmotic motor that tunes the thickness, spacing, and refractive index of the tunable, membrane-bound Bragg lamellae in the iridocytes of the loliginid squids. The tunable reflectin proteins, characterized by a variable number of highly conserved peptide domains interspersed with positively charged linker segments, are restricted in intra- and inter-chain contacts by Coulombic repulsion. Physiologically, this inhibition is progressively overcome by charge-neutralizati...
P180 Moving onto plan C: Finding detours when DSA creates a roadblock to bone marrow transplantation

Aim This case study illustrates potential avenues to consider when identifying hematopoietic stem cell donor options for HLA sensitized patients. Methods HLA typing was performed using reverse sequence specific oligonucleotide probe hybridization assays (One Lambda, Inc.) and Sanger sequence base typing assays (local and commercial kits). HLA-specific antibody was assessed using class I and class II phenotypes (Lifecodes®, Immucor) and single antigen panels (One Lambda Inc.). Results The presence of donor specific antibody (DSA) can adversely impact the likelihood of bone marrow engraftment depending on the specificity and strength of the DSA. DSA assessment and monitoring is becoming crucial as centers are utilizing HLA mismatched donors. In the last 5 years, 60–70% of the overall allogeneic bone marrow transplants at our center utilized HLA mismatched donors. In a majority of our sensitized patients, the availability of multiple eligible donors allowed for either the avoidance of DSA or the minimization of DSA to levels that did not warrant desensitization. But, in 6% of the cases evaluated in 2016, DSA caused roadblocks requiring alternate pathways. The case of a 41 year old female with Acute Lymphocytic Leukemia illustrates the “Moving onto Plan C” mantra. Plan A: A related haploidentical transplant was diverted due to crossmatch positive DSA against the patient’s four eligible donors. Plan B: An unrelated matched transplant was deterred due to DRB3*01 allele specific DSA against several 10/10 HLA loci matched donors with the DRB1*13:01/DRB3*01 association instead of patient’s DRB1*13:01/DRB3*02 association. Plan C: An unrelated mismatched donor search was initiated to identify 9/10 HLA loci matched donors with a DRB1 mismatch likely to avoid the patient’s broad specificity and eliminate the potential of a DRB3*01 typed donor. Conclusion Even though there is a low incidence of patients requiring an alternate route due to DSA, the impact of the DSA is life-threatening to the individuals in this cohort. With the increase of HLA mismatched transplants, there is a greater need for initial HLA antibody assessments, continual HLA antibody monitoring, alternative back-up plans and creative solutions in order to offer all patients the best chance of survival.
Misdirections in Informed Consent — Impediments to Health Care Innovation

Many ethicists analyzing the Common Rule are more forgiving than IRBs of waivers of informed consent in low-risk studies. Several sources of misdirection in defining “adverse effects on rights and welfare” create unnecessary obstacles to quality-improvement efforts.
Evaluating the impact of training data pixel level buffering on area sampling frame stratification results and crop estimates

Area Sampling Frames are used for surveys including crop acreage and yield, forests, and natural resource inventories and are the foundation of the statistical program of the USDA National Agricultural Statistics Service (NASS) and many statistical survey programs around the world. An automated area frame stratification method was recently implemented into NASS operations, which is based on the objective calculation of percent cultivation derived from the NASS geospatial Cropland Data Layers (CDLs). While autostratification consistently outperforms manual stratification in cultivated areas, we found that CDL-based pixel counting estimation consistently underestimated crop acreage. Previous research indicates that CDL classification accuracy is affected by training data pixel level buffering. We hypothesize that training data pixel level buffering will also affect the CDL based auto-stratification results and crop acreage estimation. This paper evaluates the impact of training data buffering on area frame stratification results and crop estimates. Preliminary results indicate that the crop acreage underestimation can be directly attributed to the training data pixel level buffering procedure.
US grand strategy after the Cold War: Can realism explain it? Should realism guide it?:

This article uses realism to explain past US grand strategy and prescribe what it should be today. Throughout its history, the United States has generally acted as realism depicts. The end of the C...
Astromech robots in Star Wars

What R2D2 and BB-8, the lovable astromechs from the Star Wars movies, can tell us about real robots.
Combined and Alternating Topical Steroids and Food Elimination Diet for the Treatment of Eosinophilic Esophagitis

Few studies have examined combined or alternating treatment algorithms in eosinophilic esophagitis. We conducted a retrospective cohort study to ascertain the efficacy and adherence to a combined and alternating treatment approach with topical corticosteroids and 2-food elimination diet for pediatric EoE. Patients were prescribed a 2-food elimination diet (milk and soy) and topical corticosteroid (fluticasone or oral viscous budesonide) for 3 months, after which the steroid was discontinued and 2-food elimination diet continued for 3 months. An EGD was performed at baseline, 3 and 6 months. Clinical, endoscopic, and histologic data were extracted from electronic medical records. Nonparametric tests assessed adherence and outcomes. Twenty-nine eosinophilic esophagitis cases were included (mean age 11.5 years, 61% male). Complete adherence to combined therapy and 2-food elimination diet alone was 75 and 79%, respectively. Median eosinophil counts decreased from 51 to 2 eosinophils/hpf (p < 0.001) after combined treatment and rebounded to 31 (p = 0.07) after 2FED alone. Dysphagia improved after both the combined and 2-food elimination diet alone treatment approaches (52 vs. 11% and 10%; p = 0.001, 0.005). Nonsignificant improvements in endoscopic findings were documented across the length of follow-up. An initial combined treatment approach resulted in significant improvements in symptoms and histologic findings. While symptomatic improvements continued with 2-food elimination diet alone, the histologic improvement was not maintained. While loss to follow-up may obscure the efficacy of 2-food elimination diet alone, a combined/alternating treatment approach merits assessment in a larger prospective study.
Pediatric Sloughing Esophagitis: A Case Report and Discussion.

Background: Sloughing esophagitis is an uncommon entity with an unclear pathogenesis characterized by desquamating sheets of squamous mucosa. It has been associated with bullous dermatologic disord...
Peptide hormones as tumor markers in lung cancer patients.

Clinicians have long sought simple, reproducible, and specific laboratory tests to detect malignant neoplasms early and monitor their course. In this regard, a variety of tumor products have been termed biomarkers, since their estimation in blood or other body fluids may indicate the existence of a malignancy and the body burden of tumor. In addition, the study of these substances may shed light on the origin, histogenesis, biological behavior, and interrelationships of the tumor cells producing them. Such biomarkers include several polypeptide hormones, enzymes, biogenic amines, and tumor-associated antigens. To be useful to the clinician, an ideal tumor marker should have the following characteristics 1 It should be produced only by tumor cells 2 Its concentration in blood or urine should reflect the body burden of tumor 3 Measurement should be sensitive enough to detect microscopic or subclinical disease 4 The assay should be convenient, inexpensive, and reproducible 5 The marker should occur with sufficient frequency to make measurement worthwhile 6 The practical value of the marker will depend on the availability of effective treatment for the cancer.
Conflicting Views of Medical Necessity: The Moran Case

An ethical case that was eventually decided in the US Supreme Court involves the right of patients to request an independent third-party review if their HMO refuses to authorize treatments or procedures deemed medically necessary. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.