Negation-Limited Complexity of Parity and Inverters

In negation-limited complexity, one considers circuits with a limited number of NOT gates, being motivated by the gap in our understanding of monotone versus general circuit complexity, and hoping to better understand the power of NOT gates. We give improved lower bounds for the size (the number of AND/OR/NOT) of negation-limited circuits computing Parity and for the size of negation-limited inverters. An inverter is a circuit with inputs x ₁,…,x _n and outputs ¬ x ₁,…,¬ x _n . We show that: (a) for n=2 ^r ?1, circuits computing Parity with r?1 NOT gates have size at least 6n?log?₂(n+1)?O(1), and (b) for n=2 ^r ?1, inverters with r NOT gates have size at least 8n?log?₂(n+1)?O(1). We derive our bounds above by considering the minimum size of a circuit with at most r NOT gates that computes Parity for sorted inputs x ₁≥???≥x _n . For an arbitrary r, we completely determine the minimum size. It is 2n?r?2 for odd n and 2n?r?1 for even n for ?log?₂(n+1)??1≤r≤n/2, and it is ?3n/2??1 for r≥n/2. We also determine the minimum size of an inverter for sorted inputs with at most r NOT gates. It is 4n?3r for ?log?₂(n+1)?≤r≤n. In particular, the negation-limited inverter for sorted inputs due to Fischer, which is a core component in all the known constructions of negation-limited inverters, is shown to have the minimum possible size. Our fairly simple lower bound proofs use gate elimination arguments in a somewhat novel way.     

Avoiding Routing Loops on the Internet

Suppose that some particular link in the Internet is currently congested. A natural solution is to try to make packets bypass that link. This can be done by increasing the cost of that link intentionally, say from a ₁ to a ₂, since the Internet uses shortest-path routing. Unfortunately, however, this often causes temporary loops for packet traveling, called routing loops. In this paper we show that routing loops can be avoided by increasing the cost of the link not directly from a ₁ to a ₂ but through an intermediate value, a ₃, i.e., from a ₁ to a ₃ and then to a ₂. We may need several intermediate values. We show that in this case the greedy strategy, namely, raising the cost as much as possible in each step, is optimal.     

Aging and Clonal Behavior of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging.     

Distribution of ytterbium (Yb) in cells of Streptomyces sp. YB-1 which can accumulate Yb, and reusability of cells and cell membrane as bioadsorbent for Yb

The cells of Streptomyces sp. YB-1 adsorbed 4-6 mg ytterbium (Yb) per g dry weight. The Yb contents of the cell wall fraction, cell-free extract, and cell membrane fraction were 11%, 2%, and 87%, respectively. The Yb content in the cell membrane fraction was 20-25 mg per g dry weight. The adsorbed Yb could be quantitatively desorbed by treating the cell membrane fraction with 1 mM EDTA and 1 M HCl at 37 degrees C for 4 h. Treatment with 1 M NaOH caused Yb desorption to some extent. Treatments with proteinase K, lysozyme, 0.5% Triton X-100, 0.4% sodium dodecyl sulfate, and 1 M NaCl did not cause Yb desorption. Elemental analysis of Yb-adsorbed materials after removal of proteins and then extraction of lipids from the membrane fraction revealed that the molar ratio of Yb and P in the materials was about 1:1. The cells and the membrane fraction could be used repeatedly as a bioadsorbent for Yb.     

Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability

BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.     

Cardiac malignant pheochromocytoma with bone metastases

A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.     

Molecular structure of La3+-induced methanol dehydrogenase-like protein in Methylobacterium radiotolerans

La(3+) and not Ca(2+) increases methanol dehydrogenase (MDH) activity in Methylobacterium radiotolerans NBRC15690. La(3+)- and Ca(2+)-MDH-like proteins were found to be homodimeric (α(2)) and heterotetrameric (α(2)β(2)), respectively. N-terminal amino acid sequences of these proteins revealed that La(3+)- and Ca(2+)-MDH-like proteins were encoded by xoxF and mxaFI, respectively.     

Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency

The effect of the choice of maternal age-specific prevalence curve on the model predicted Down syndrome detection rate was examined. All 19 published regression curves from 11 birth prevalence series in four meta-analyses were included. The detection rate for a five per cent false-positive rate was estimated for three combinations of markers. For free beta human chorionic gonadotropin and alpha-fetoprotein the lowest predicted detection rate was 62.3 per cent and the highest 64.1 per cent, a range of 1.8 per cent. When unconjugated oestriol was added as a third marker it was 65.6-67.3 per cent, a 1.7 per cent range, and when inhibin A was the fourth marker the detection rate was 72.0-73.4 per cent, a 1.4 per cent range. The number of series included in the regression had the biggest effect: when the authors had used a subset thought to have the highest ascertainment the predicted detection rate generally increased. The type of regression equation used and restrictions on the age range over which the regression was performed were less important factors. The effect of the choice of curve on the predicted increase in detection achieved by incorporating additional markers was relatively small: 3.1-3.3 per cent for unconjugated oestriol and a further 6.1-6.5 per cent for inhibin A. This analysis shows that the model inaccuracy caused by the maternal age curve is not small but is unlikely to be large enough to influence Down syndrome screening policy decisions.