Combinatorial Assortment Optimization

Assortment optimization refers to the problem of designing a slate of products to offer potential customers, such as stocking the shelves in a convenience store. The price of each product is fixed in advance, and a probabilistic choice function describes which product a customer will choose from any given subset. We introduce the combinatorial assortment problem, where each customer may select a bundle of products. We consider a model of consumer choice where the relative value of different bundles is described by a valuation function, while individual customers may differ in their absolute willingness to pay, and study the complexity of the resulting optimization problem. We show that any sub-polynomial approximation to the problem requires exponentially many demand queries when the valuation function is XOS, and that no FPTAS exists even for succinctly-representable submodular valuations. On the positive side, we show how to obtain constant approximations under a "well-priced" condition, where each product's price is sufficiently high. We also provide an exact algorithm for $k$-additive valuations, and show how to extend our results to a learning setting where the seller must infer the customers' preferences from their purchasing behavior

Src Stimulates Abl-dependent Phosphorylation of the Guanine Exchange Factor Net1a to Promote Its Cytosolic Localization and Cell Motility

The neuroepithelial cell transforming gene 1 (Net1) is a guanine nucleotide exchange factor for the small GTPase RhoA that promotes cancer cell motility and metastasis. Two isoforms of Net1 exist, Net1 and Net1A, both of which are sequestered in the nucleus in quiescent cells to prevent aberrant RhoA activation. Many cell motility stimuli drive cytosolic relocalization of Net1A, but mechanisms controlling this event are not fully understood. Here, we demonstrate that epithelial growth factor stimulates protein kinase Src- and Abl1-dependent phosphorylation of Net1A to promote its cytosolic localization. We show that Abl1 efficiently phosphorylates Net1A on Y373, and that phenylalanine substitution of Y373 prevents Net1A cytosolic localization. Furthermore, we found that Abl1-driven cytosolic localization of Net1A does not require S52, which is a phosphorylation site of a different kinase, c-Jun N-terminal kinase, that inhibits nuclear import of Net1A. However, we did find that MKK7-stimulated cytosolic localization of Net1A does require Y373. We also demonstrate that aspartate substitution at Y373 is sufficient to promote Net1A cytosolic accumulation, and expression of Net1A Y373D potentiates epithelial growth factor-stimulated RhoA activation, downstream myosin light chain 2 phosphorylation, and F-actin accumulation. Moreover, we show that expression of Net1A Y373D in breast cancer cells also significantly increases cell motility and Matrigel invasion. Finally, we show that Net1A is required for Abl1-stimulated cell motility, which is rescued by expression of Net1A Y373D, but not Net1A Y373F. Taken together, this work demonstrates a novel mechanism controlling Net1A subcellular localization to regulate RhoA-dependent cell motility and invasion

Rumput Laut (Ulva lactuca) sebagai Pakan Substitusi Sapi Bali Sapihan di Musim Kemarau dengan Level Energi yang Berbeda

Penelitian dilakukan untuk mengetahui kualitas dan pengaruh rumput laut (Ulva lactuca) sebagai pakan substitusi untuk sapi Bali sapihan di musim kemarau dengan level energi yang berbeda. Penelitian dilakukan dua tahap yaitu perlakuan in vitro untuk mengetahui level ideal pemberian tepung U. lactuca dengan perlakuan RA = hay rumput alam; RAK = RA+konsentrat; RAKU5 =RAK+U. lactuca 5%; RAKU10= RAK+U. lactuca 10%; RAKU15= RAK+U. lactuca 15%; RAKU20= RAK+U. lactuca 20%. Tahap kedua menggunakan rancangan Bujur Sangkar Latin dengan perlakuan R1 = EM 7,3 MJ, R2 = EM 8 MJ dan R3 = EM 8,7 MJ. Hasil penelitian menunjukkan bahwa level ideal pemberian yang dapat digunakan adalah 15% dengan nilai kecernaan bahan kering dan bahan organik tertinggi yaitu 77,79 dan 78,56%.  Tahap kedua yaitu pemberian tepung U. lactuca sebanyak 15% dari total ransum dengan level energy yang berbeda untuk sembilan ekor sapi Bali sapihan dengan tujuan mengetahui tingkat konsumsi dan kecernaan dengan perlakuan EM R1= 7,3 MJ; R= 8 MJ; dan R3= 8,7 MJ. Hasil penelitian menunjukkan bahwa substitusi tepung U. lactuca sebanyak 15% tidak memberikan pengaruh negatif terhadap konsumsi dan kecernaan. Hasil sidik ragam menunjukkan ransum dengan energi 8 MJ memiliki konsumsi dan kecernaan yang sama dengan energi 8,7 MJ namun lebih tinggi dibandingkan dengan ransum  berenergi 7,3 MJ

The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent

Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease

Hypertensive Disorders of Pregnancy are Associated with Differences in Maternal Serum Concentrations of Arachidonic Acid Metabolites

Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, chronic hypertension, and preeclampsia, are a significant cause of maternal morbidity and mortality in the United States. Dysregulation of inflammation is thought to play a role in the development of HDP. Maternal diet has the potential to alter the risk of HDP by modulating inflammation. Arachidonic acid (AA) is a dietary polyunsaturated fatty acid which can be metabolized into both pro- and anti-inflammatory bioactive metabolites. Significance of Problem: HDP places women and their infants at risk for potentially severe pregnancy complications including placental abruption, embolism, end-organ failure, or death. Few treatments are currently available for HDP. Question: The objective of this study was to describe how maternal AA metabolites serum concentrations are associated with diagnosis of HDP. Experimental Design: Serum was collected from 121 pregnant women admitted to the labor and delivery unit at Nebraska Medical Center. Women were divided into normotensive or hypertensive groups based on definitions from the American College of Obstetricians and Gynecologists (ACOG). Concentrations of AA metabolites were measured using liquid chromatography-mass spectrometry. Descriptive statistics were generated, and Mann-Whitney U tests were used to compare metabolite concentrations between groups. Results: Women with HDP had significant higher serum concentrations of PGF2α (p=0.02) and 15-HETE (p=0.04), two metabolites with known inflammatory and vasoconstrictive properties. Women with HDP had significantly lower serum concentrations of 8(9)-DiHET (p=0.04), 11(12)-DiHET (p=0.04), and 14(15)-DiHET (p=0.001), which are all associated with vasodilation. Unexpectantly, hypertensive mothers also had lower serum concentrations of 5-HETE (p=0.02), which is associated with vasoconstriction. Conclusion: Overall, our study reveals that mothers diagnosed with HDP had significantly higher serum concentrations of vasoconstrictive AA metabolites and significantly lower serum concentrations of vasodilating AA metabolites compared to normotensive mothers. Future directions include analyzing differences in maternal metabolite profile separately for mothers with chronic hypertension, gestational hypertension, and preeclampsia compared to normotensive mothers. Results from these analyses will guide nutritional recommendations for women at risk of developing HDP.https://digitalcommons.unmc.edu/chri_forum/1062/thumbnail.jp

High-speed >90% quantum-efficiency p–i–n photodiodes with a resonance wavelength adjustable in the 795–835 nm range

Cataloged from PDF version of article.We report GaAs/AlGaAs-based high-speed, high-efficiency, resonant cavity enhanced p–i–nphotodiodes. The devices were fabricated by using a microwave-compatible fabrication process. By using a postprocess recess etch, we tuned the resonance wavelength from 835 to 795 nm while keeping the peak efficiencies above 90%. The maximum quantum efficiency was 92% at a resonance wavelength of 823 nm. The photodiode had an experimental setup-limited temporal response of 12 ps. When the system response is deconvolved, the 3 dB bandwidth corresponds to 50 GHz, which is in good agreement with our theoretical calculations. © 1999 American Institute of Physic

Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation:A retrospective cohort study

Aims: Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole-blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model. Methods: Data of pregnant women using a twice-daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness-of-fit plots, visual predictive checks and a bootstrap analysis. Results: A total of 260 whole-blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance.Conclusions: Tacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole-blood tacrolimus predose concentrations during pregnancy, increasing the dose is required.</p

Palaeozoic-Recent geological development and uplift of the Amanos Mountains (S Turkey) in the critically located northwesternmost corner of the Arabian continent

<p>We have carried out a several-year-long study of the Amanos Mountains, on the basis of which we present new sedimentary and structural evidence, which we combine with existing data, to produce the first comprehensive synthesis in the regional geological setting. The ca. N-S-trending Amanos Mountains are located at the northwesternmost edge of the Arabian plate, near the intersection of the African and Eurasian plates. Mixed siliciclastic-carbonate sediments accumulated on the north-Gondwana margin during the Palaeozoic. Triassic rift-related sedimentation was followed by platform carbonate deposition during Jurassic-Cretaceous. Late Cretaceous was characterised by platform collapse and southward emplacement of melanges and a supra-subduction zone ophiolite. Latest Cretaceous transgressive shallow-water carbonates gave way to deeper-water deposits during Palaeocene-Eocene. Eocene southward compression, reflecting initial collision, resulted in open folding, reverse faulting and duplexing. Fluvial, lagoonal and shallow-marine carbonates accumulated during Late Oligocene(?)-Early Miocene, associated with basaltic magmatism. Intensifying collision during Mid-Miocene initiated a foreland basin that then infilled with deep-water siliciclastic gravity flows. Late Miocene-Early Pliocene compression created mountain-sized folds and thrusts, verging E in the north but SE in the south. The resulting surface uplift triggered deposition of huge alluvial outwash fans in the west. Smaller alluvial fans formed along both mountain flanks during the Pleistocene after major surface uplift ended. Pliocene-Pleistocene alluvium was tilted towards the mountain front in the west. Strike-slip/transtension along the East Anatolian Transform Fault and localised sub-horizontal Quaternary basaltic volcanism in the region reflect regional transtension during Late Pliocene-Pleistocene (<4 Ma).</p

An Obscure Case of Hepatic Subcapsular Hematoma

Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma