Parameterizing by the Number of Numbers

The usefulness of parameterized algorithmics has often depended on what Niedermeier has called, "the art of problem parameterization". In this paper we introduce and explore a novel but general form of parameterization: the number of numbers. Several classic numerical problems, such as Subset Sum, Partition, 3-Partition, Numerical 3-Dimensional Matching, and Numerical Matching with Target Sums, have multisets of integers as input. We initiate the study of parameterizing these problems by the number of distinct integers in the input. We rely on an FPT result for ILPF to show that all the above-mentioned problems are fixed-parameter tractable when parameterized in this way. In various applied settings, problem inputs often consist in part of multisets of integers or multisets of weighted objects (such as edges in a graph, or jobs to be scheduled). Such number-of-numbers parameterized problems often reduce to subproblems about transition systems of various kinds, parameterized by the size of the system description. We consider several core problems of this kind relevant to number-of-numbers parameterization. Our main hardness result considers the problem: given a non-deterministic Mealy machine M (a finite state automaton outputting a letter on each transition), an input word x, and a census requirement c for the output word specifying how many times each letter of the output alphabet should be written, decide whether there exists a computation of M reading x that outputs a word y that meets the requirement c. We show that this problem is hard for W[1]. If the question is whether there exists an input word x such that a computation of M on x outputs a word that meets c, the problem becomes fixed-parameter tractable

Combinatorial Voter Control in Elections

Voter control problems model situations such as an external agent trying to affect the result of an election by adding voters, for example by convincing some voters to vote who would otherwise not attend the election. Traditionally, voters are added one at a time, with the goal of making a distinguished alternative win by adding a minimum number of voters. In this paper, we initiate the study of combinatorial variants of control by adding voters: In our setting, when we choose to add a voter~$v$, we also have to add a whole bundle $\kappa(v)$ of voters associated with $v$. We study the computational complexity of this problem for two of the most basic voting rules, namely the Plurality rule and the Condorcet rule.Comment: An extended abstract appears in MFCS 201

NF-κB and its role in checkpoint control

Nuclear factor-κB (NF-κB) has been described as one of the most important molecules linking inflammation to cancer. More recently, it has become clear that NF-κB is also involved in the regulation of immune checkpoint expression. Therapeutic approaches targeting immune checkpoint molecules, enabling the immune system to initiate immune responses against tumor cells, constitute a key breakthrough in cancer treatment. This review discusses recent evidence for an association of NF-κB and immune checkpoint expression and examines the therapeutic potential of inhibitors targeting either NF-κB directly or molecules involved in NF-κB regulation in combination with immune checkpoint blockade

Refinement of Miocene sea level and monsoon events from the sedimentary archive of the Maldives (Indian Ocean)

International Ocean Discovery Program (IODP) Expedition 359 cored sediments from eight borehole locations in the carbonate platform of the Maldives in the Indian Ocean. The expedition set out to unravel the timing of Neogene climate changes, in particular the evolution of the South Asian monsoon and fluctuations of the sea level. The timing of these changes are assessed by dating resultant sedimentary alterations that mark stratigraphic turning points in the Neogene Maldives platform system. The first four turning points during the early and middle Miocene are related to sea-level changes. These are reliably recorded in the stratigraphy of the carbonate sequences in which sequence boundaries provide the ages of the sea-level lowstand. Phases of aggradational platform growth give precise age brackets of long-term sea-level high stands during the early Miocene and the early to middle Miocene Climate Optimum that is dated here between 17 to 15.1 Ma. The subsequent middle Miocene cooling coincident with the eastern Antarctic ice sheet expansion resulted in a long-term lowering of sea level that is reflected by a progradational platform growth. The change in platform architecture from aggradation to progradation marks this turning point at 15.1 Ma. An abrupt change in sedimentation pattern is recognized across the entire archipelago at a sequence boundary dated as 12.9–13 Ma. At this turning point, the platform sedimentation switched to a current-controlled mode when the monsoon-wind-driven circulation started in the Indian Ocean. The similar age of the onset of drift deposition from monsoon-wind-driven circulation across the entire archipelago indicates an abrupt onset of monsoon winds in the Indian Ocean. Ten unconformities dissect the drift sequences, attesting changes in current strength or direction that are likely caused by the combined product of changes in the monsoon-wind intensity and sea level fluctuations in the last 13 Ma. A major shift in the drift packages is dated with 3.8 Ma that coincides with the end of stepwise platform drowning and a reduction of the oxygen minimum zone in the Inner Sea. The strata of the Maldives platform provides a detailed record of the extrinsic controlling factors on carbonate platform growth through time. This potential of carbonate platforms for dating the Neogene climate and current changes has been exploited in other platforms drilled by the Ocean Drilling Program. For example, Great Bahama Bank, the Queensland Plateau, and the platforms on the Marion Plateau show similar histories with sediment architectures driven by sea level in their early history (early to middle Miocene) replaced by current-driven drowning or partial drowning during their later history (Late Miocene). In all three platform systems, the influence of currents on sedimentations is reported between 11 and 13 Ma

Strong structural and electronic coupling in metavalent PbS moire superlattices

Moire superlattices are twisted bilayer materials, in which the tunable interlayer quantum confinement offers access to new physics and novel device functionalities. Previously, moire superlattices were built exclusively using materials with weak van der Waals interactions and synthesizing moire superlattices with strong interlayer chemical bonding was considered to be impractical. Here using lead sulfide (PbS) as an example, we report a strategy for synthesizing of moire superlattices coupled by strong chemical bonding. We use water-soluble ligands as a removable template to obtain free-standing ultra-thin PbS nanosheets and assemble them into direct-contact bilayers with various twist angles. Atomic-resolution imaging shows the moire periodic structural reconstruction at superlattice interface, due to the strong metavalent coupling. Electron energy loss spectroscopy and theoretical calculations collectively reveal the twist angle26 dependent electronic structure, especially the emergent separation of flat bands at small twist angles. The localized states of flat bands are similar to well-arranged quantum dots, promising an application in devices. This study opens a new door to the exploration of deep energy modulations within moire superlattices alternative to van der Waals twistronics

Mangarara Formation: exhumed remnants of a middle Miocene, temperate carbonate, submarine channel-fan system on the eastern margin of Taranaki Basin, New Zealand

The middle Miocene Mangarara Formation is a thin (1–60 m), laterally discontinuous unit of moderately to highly calcareous (40–90%) facies of sandy to pure limestone, bioclastic sandstone, and conglomerate that crops out in a few valleys in North Taranaki across the transition from King Country Basin into offshore Taranaki Basin. The unit occurs within hemipelagic (slope) mudstone of Manganui Formation, is stratigraphically associated with redeposited sandstone of Moki Formation, and is overlain by redeposited volcaniclastic sandstone of Mohakatino Formation. The calcareous facies of the Mangarara Formation are interpreted to be mainly mass-emplaced deposits having channelised and sheet-like geometries, sedimentary structures supportive of redeposition, mixed environment fossil associations, and stratigraphic enclosure within bathyal mudrocks and flysch. The carbonate component of the deposits consists mainly of bivalves, larger benthic foraminifers (especially Amphistegina), coralline red algae including rhodoliths (Lithothamnion and Mesophyllum), and bryozoans, a warm-temperate, shallow marine skeletal association. While sediment derivation was partly from an eastern contemporary shelf, the bulk of the skeletal carbonate is inferred to have been sourced from shoal carbonate factories around and upon isolated basement highs (Patea-Tongaporutu High) to the south. The Mangarara sediments were redeposited within slope gullies and broad open submarine channels and lobes in the vicinity of the channel-lobe transition zone of a submarine fan system. Different phases of sediment transport and deposition (lateral-accretion and aggradation stages) are identified in the channel infilling. Dual fan systems likely co-existed, one dominating and predominantly siliciclastic in nature (Moki Formation), and the other infrequent and involving the temperate calcareous deposits of Mangarara Formation. The Mangarara Formation is an outcrop analogue for middle Miocene-age carbonate slope-fan deposits elsewhere in subsurface Taranaki Basin, New Zealand

(Total) Vector Domination for Graphs with Bounded Branchwidth

Given a graph $G=(V,E)$ of order $n$ and an $n$-dimensional non-negative vector $d=(d(1),d(2),\ldots,d(n))$, called demand vector, the vector domination (resp., total vector domination) is the problem of finding a minimum $S\subseteq V$ such that every vertex $v$ in $V\setminus S$ (resp., in $V$) has at least $d(v)$ neighbors in $S$. The (total) vector domination is a generalization of many dominating set type problems, e.g., the dominating set problem, the $k$-tuple dominating set problem (this $k$ is different from the solution size), and so on, and its approximability and inapproximability have been studied under this general framework. In this paper, we show that a (total) vector domination of graphs with bounded branchwidth can be solved in polynomial time. This implies that the problem is polynomially solvable also for graphs with bounded treewidth. Consequently, the (total) vector domination problem for a planar graph is subexponential fixed-parameter tractable with respectto $k$, where $k$ is the size of solution.Comment: 16 page

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressive cytokines, including IL-10, IL-35, TGF-β, granzyme B, and adenosine or dampen effector TILs by intercellular contacts. Multiple Breg phenotypes have been discovered in human and mouse cancer models. However, when compartmentalized within a tertiary lymphoid structure (TLS), B cells predominantly play anti-tumor effects. A mature TLS contains a CD20+ B cell zone with several important types of B cells, including germinal-center like B cells, antibody-secreting plasma cells, and memory B cells. They kill tumor cells via antibody-dependent cytotoxicity and phagocytosis, and local complement activation effects. TLSs are also privileged sites for local T and B cell coordination and activation. Nonetheless, in some cases, TLSs may serve as a niche for hidden tumor cells and indicate a bad prognosis. Thus, TIL-B cells exhibit bidirectional immune-modulatory activity and are responsive to a variety of immunotherapies. In this review, we discuss the functional distinctions between immunosuppressive Breg cells and immunogenic effector B cells that mature within TLSs with the focus on tumors of HNSCC patients. Additionally, we review contemporary immunotherapies that aim to target TIL-B cells. For the development of innovative therapeutic approaches to complement T-cell-based immunotherapy, a full understanding of either effector B cells or Breg cells is necessary

A Cretaceous carbonate delta drift in the Montagna della Maiella, Italy

The Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is compared to newly discovered contourite drifts in the Maldives. Like the drift deposits in the Maldives, the Orfento Formation fills a channel and builds a Miocene delta-shaped and mounded sedimentary body in the basin that is similar in size to the approximately 350 km 2 large coarse-grained bioclastic Miocene delta drifts in the Maldives. The composition of the bioclastic wedge of the Orfento Formation is also exclusively bioclastic debris sourced from the shallow-water areas and reworked clasts of the Orfento Formation itself. In the near mud-free succession, age-diagnostic fossils are sparse. The depositional textures vary from wackestone to float-rudstone and breccia/conglomerates, but rocks with grainstone and rudstone textures are the most common facies. In the channel, lensoid convex-upward breccias, cross-cutting channelized beds and thick grainstone lobes with abundant scours indicate alternating erosion and deposition from a high-energy current. In the basin, the mounded sedimentary body contains lobes with a divergent progradational geometry. The lobes are built by decametre thick composite megabeds consisting of sigmoidal clinoforms that typically have a channelized topset, a grainy foreset and a fine-grained bottomset with abundant irregular angular clasts. Up to 30 m thick channels filled with intraformational breccias and coarse grainstones pinch out downslope between the megabeds. In the distal portion of the wedge, stacked grainstone beds with foresets and reworked intraclasts document continuous sediment reworking and migration. The bioclastic wedge of the Orfento Formation has been variously interpreted as a succession of sea-level controlled slope deposits, a shoaling shoreface complex, or a carbonate tidal delta. Current-controlled delta drifts in the Maldives, however, offer a new interpretation because of their similarity in architecture and composition. These similarities include: (i) a feeder channel opening into the basin; (ii) an excavation moat at the exit of the channel; (iii) an overall mounded geometry with an apex that is in shallower water depth than the source channel; (iv) progradation of stacked lobes; (v) channels that pinch out in a basinward direction; and (vi) smaller channelized intervals that are arranged in a radial pattern. As a result, the Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is here interpreted as a carbonate delta drift

On Structural Parameterizations of the Bounded-Degree Vertex Deletion Problem

We study the parameterized complexity of the Bounded-Degree Vertex Deletion problem (BDD), where the aim is to find a maximum induced subgraph whose maximum degree is below a given degree bound. Our focus lies on parameters that measure the structural properties of the input instance. We first show that the problem is W[1]-hard parameterized by a wide range of fairly restrictive structural parameters such as the feedback vertex set number, pathwidth, treedepth, and even the size of a minimum vertex deletion set into graphs of pathwidth and treedepth at most three. We thereby resolve an open question stated in Betzler, Bredereck, Niedermeier and Uhlmann (2012) concerning the complexity of BDD parameterized by the feedback vertex set number. On the positive side, we obtain fixed-parameter algorithms for the problem with respect to the decompositional parameter treecut width and a novel problem-specific parameter called the core fracture number