Covering Points by Disjoint Boxes with Outliers

For a set of n points in the plane, we consider the axis--aligned (p,k)-Box Covering problem: Find p axis-aligned, pairwise-disjoint boxes that together contain n-k points. In this paper, we consider the boxes to be either squares or rectangles, and we want to minimize the area of the largest box. For general p we show that the problem is NP-hard for both squares and rectangles. For a small, fixed number p, we give algorithms that find the solution in the following running times: For squares we have O(n+k log k) time for p=1, and O(n log n+k^p log^p k time for p = 2,3. For rectangles we get O(n + k^3) for p = 1 and O(n log n+k^{2+p} log^{p-1} k) time for p = 2,3. In all cases, our algorithms use O(n) space.Comment: updated version: - changed problem from 'cover exactly n-k points' to 'cover at least n-k points' to avoid having non-feasible solutions. Results are unchanged. - added Proof to Lemma 11, clarified some sections - corrected typos and small errors - updated affiliations of two author

UVB Induces HIF-1α-Dependent TSLP Expression via the JNK and ERK Pathways

Thymic stromal lymphopoietin (TSLP) may have a key role in the initiation and maintenance of allergic inflammatory diseases, including atopic dermatitis. The present study revealed that UVB radiation exposure could induce TSLP expression in human keratinocytes and a human skin equivalent model. In addition, we investigated the regulatory mechanism of UVB-induced TSLP expression in keratinocytes. TSLP expression was upregulated by transfection with pcDNA3–hypoxia-inducible factor (HIF)-1α (P402A and P564A), which stably expresses HIF-1α protein. UVB-induced TSLP induction in keratinocytes was suppressed in the treatment of mitogen-activated protein kinase inhibitors or small interfering RNAs against HIF-1α. The results of chromatin immunoprecipitation assays indicate the direct involvement of HIF-1α in UVB-mediated TSLP induction. Taken together, these findings indicate that UVB exposure may increase TSLP expression through a HIF-1α-dependent mechanism via the c-JUN N-terminal kinase and extracellular signal-regulated kinase pathways in human keratinocytes. Our data showed that UVB-induced TSLP might increase secretion of the T-helper type 2–attracting chemokine (c–c motif) ligand 17 by human dendritic cells. The present study suggests an important role of HIF-1α in UVB-mediated immune response in keratinocytes

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC(50) values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the C(max) of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose

Breakdown of the interlayer coherence in twisted bilayer graphene

Coherent motion of the electrons in the Bloch states is one of the fundamental concepts of the charge conduction in solid state physics. In layered materials, however, such a condition often breaks down for the interlayer conduction, when the interlayer coupling is significantly reduced by e.g. large interlayer separation. We report that complete suppression of coherent conduction is realized even in an atomic length scale of layer separation in twisted bilayer graphene. The interlayer resistivity of twisted bilayer graphene is much higher than the c-axis resistivity of Bernal-stacked graphite, and exhibits strong dependence on temperature as well as on external electric fields. These results suggest that the graphene layers are significantly decoupled by rotation and incoherent conduction is a main transport channel between the layers of twisted bilayer graphene.Comment: 5 pages, 3 figure

Intramural gallbladder hematoma mimicking gallbladder neoplasm in a 55-year-old male patient

Hemorrhage in the gallbladder (GB) is usually associated with cholecystitis, GB neoplasm, trauma, hemobilia, and cystic artery aneurysm. Our patient had not experienced any previous abdominal trauma, and GB hemorrhage was unlikely to result from cholecystitis or bleeding diathesis. A 55-year-old male was admitted because of right upper quadrant pain. Both prothrombin time and partial thromboplastin time were normal. Abdominal computed tomography, endoscopic ultrasound and magnetic resonance cholangiopancreatography were performed. Image studies revealed GB wall thickening and an intraluminal mass. Laparoscopic cholecystectomy was performed. Upon opening the GB postoperatively, a large amount of fresh blood and old blood clot was noted. The incidence of GB hematoma is very rare. GB hematoma should always be considered in the differential diagnosis of GB tumor. In such a situation, surgical intervention is needed for further patient evaluation and management. We present a rare case of intramural GB hematoma, of which we were unable to make a definitive diagnosis preoperatively

Microstructural, Electrical and Mechanical Properties of the Al-Zn-Mg-Mn Alloy with Strontium Addition

This study investigated the improvement in the electrical conductivity and mechanical properties obtained by adjusting the amount of the Sr addition to the Al-Zn-Mg-Mn alloy. The addition of Sr formed an intermetallic compounds, and the volume fraction of the intermetallic compounds increased with increasing Sr content. As the amount of Sr added increased from 0 to 1.0 wt%, the electrical conductivity of the extruded alloy decreased to 48.9, 45.2 and 42.5% IACS. As the addition amount of Sr increased, the average grain size of the rolled alloy decreased to 55.5, 53.1 and 42.3 μm. And, the ultimate tensile strength increased to 195, 212 and 216 MPa