Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene ...cyclases (TCs) and a nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The core of 1 is a tetracyclic, cage-like, and oxygenated sesquiterpene that is connected to dimethylcadaverine via a C–N bond and is acylated with 5,5-dimethyl-l-pipecolate. The roles of all flv enzymes are established on the basis of metabolite analysis from heterologous expression.
In the Multi-Spreader Crane Scheduling Problem (MSCSP), containers with identical dimensions but variable weights are arranged along a grid. A multi-spreader crane is used to lift all the containers. ...The crane has m>1 modes. When it is in the pth mode, the crane can remove p adjacent containers along the same row at the same time as long as the total weight of the containers does not exceed the loading capacity κp. Such a lift takes hp minutes. It also takes cp,q minutes for the crane to switch from mode p to q when p≠q. The goal is to find a crane lift sequence so that the total time it takes to lift all the containers is minimized.
This paper investigates the computational complexity of MSCSP. First, we establish a connection between greedy crane lift sequences and supersequences. We then prove that MSCSP is NP-hard when the crane has three or more modes by a reduction from a version of the Shortest Common Supersequence problem. Lastly, we investigate two problems that arise naturally when heuristics are used to solve MSCSP. We show that one can be solved using dynamic programming while the other remains computationally hard. We also provide an approximation algorithm that behaves nicely when the changeover times are not much larger than the lifting times of the crane.
Identification and structure-guided optimization of a series of 4-(pyrazol-4-yl)-pyrimidines as selective CDK4/6 inhibitors is reported herein. Several potency and selectivity determinants were ...established based on the X-ray crystallographic analysis of representative compounds bound to monomeric CDK6. Significant selectivity for CDK4/6 over CDK1 and CDK2 was demonstrated with several compounds in both enzymatic and cellular assays.
Many studies have examined predictors of nurses’ intention to work in their job, including desire to quit. Intent has been a good predictor of actual turnover. Few longitudinal studies exist that ...consider regional variables.
To extend the conceptual framework of turnover research to the whole nursing workforce and determine: (1) how do demographics, region (metropolitan statistical area: MSA), movement opportunities, and work setting variables affect registered nurses’ (RNs) intent to work and desire to quit; and (2) how do demographics, MSA variables, movement opportunities, and work setting variables affect RNs’ work behavior at time 2?
Panel study using Dillman's design method.
Randomly selected national cluster sample from 40 urban geographic regions (MSAs) in 29 states of the United States.
Four thousand surveys were sent. There were 1907 female RNs under 65 (48% response rate) from year 1 of which 1348 responded at year 2 (70% response rate).
The first analyses used desire to quit (explained 65% of the variance) and intent to work from year 1 as dependent variables. Satisfaction and organizational commitment were significant negative predictors of desire to quit. In the logistic regression on intent to work, the work motivation and work–family conflict were positive and significant as well as wages (negative) and three benefit variables. In year 2, the dependent variable was working or not and if working, full-time or not. For this bivariate probit regression no attitudes influenced the work/not work decision, but MSA level variables, wages (positive) and benefits (positive) did. Organizational commitment and higher workload increased the probability of working FT.
Regional differences across markets need to be controlled and their influence investigated. In addition, attitudes as well as wages and benefits were important in certain decisions: these factors are clearly under the influence of employers.
Birkhoff’s fundamental theorem on distributive lattices states that for every distributive lattice L there is a poset PL whose lattice of down-sets is order-isomorphic to L. Let G(L) denote the cover ...graph of L. In this paper, we consider the following problems: suppose we are simply given PL. How do we compute the eccentricity of an element of L in G(L)? How about a center and the radius of G(L)? While eccentricity, center and radius computations have long been studied for various classes of graphs, our problems are different in that we are not given the graph explicitly; instead, we only have a structure that implicitly describes the graph. By making use of the comparability graph of PL, we show that all the said problems can be solved efficiently. One of the implications of these results is that a center stable matching, a kind of fair stable matching, can be computed in polynomial time.
A vertex
k
-
coloring of graph
G
is
distinguishing if the only automorphism of
G
that preserves the colors is the identity map. It is
proper-distinguishing if the coloring is both proper and ...distinguishing. The
distinguishing number of
G
,
D
(
G
)
, is the smallest integer
k
so that
G
has a distinguishing
k
-coloring; the
distinguishing chromatic number of
G
,
χ
D
(
G
)
, is defined similarly.
It has been shown recently that the distinguishing number of a planar graph can be determined efficiently by counting a related parameter–the number of inequivalent distinguishing colorings of the graph. In this paper, we demonstrate that the same technique can be used to compute the distinguishing number
and the distinguishing chromatic number of an interval graph. We make use of PQ-trees, a classic data structure that has been used to recognize and test the isomorphism of interval graphs; our algorithms run in
O
(
n
3
log
3
n
)
time for graphs with
n
vertices. We also prove a number of results regarding the computational complexity of determining a graph’s distinguishing chromatic number.
All nuclear-encoded mRNAs contain a 5' cap structure (m7GpppN, where N is any nucleotide), which is recognized by the eukaryotic translation initiation factor 4E (eIF4E) subunit of the eIF4F complex. ...The eIF4E-binding proteins constitute a family of three polypeptides that reversibly repress cap-dependent translation by binding to eIF4E, thus preventing the formation of the eIF4F complex. We investigated the biological function of 4E-BP1 by disrupting its gene (Eif4ebp1) in the mouse. Eif4ebp1-/- mice manifest markedly smaller white fat pads than wild-type animals, and knockout males display an increase in metabolic rate. The males' white adipose tissue contains cells that exhibit the distinctive multilocular appearance of brown adipocytes, and expresses the uncoupling protein 1 (UCP1), a specific marker of brown fat. Consistent with these observations, translation of the peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC1), a transcriptional co-activator implicated in mitochondrial biogenesis and adaptive thermogenesis, is increased in white adipose tissue of Eif4ebp1-/- mice. These findings demonstrate that 4E-BP1 is a novel regulator of adipogenesis and metabolism in mammals.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Motivated by the observation that most companies are more likely to consider job applicants referred by their employees than those who applied on their own, Arcaute and Vassilvitskii modeled a job ...market that integrates social networks into stable matchings in an interesting way. We call their model HR+SN because an instance of their model is an ordered pair (I, G) where I is a typical instance of the Hospital/Residents problem (HR) and G is a graph that describes the social network (SN) of the residents in I. A matching p, of hospitals and residents has a local blocking pair (h, r) if (h, r) is a blocking pair of ii, and there is a resident r' such that r' is simultaneously an employee of h in the matching and a neighbor of r in G. Such a pair is likely to compromise the matching because the participants have access to each other through r': r can give her resume to r' who can then forward it to h. A locally stable matching is a matching with no local blocking pairs. The cardinality of the locally stable matchings of I can vary. This paper presents a variety of results on computing a locally stable matching with maximum cardinality.
An edge-labeling
λ
for a directed graph
G
has a
weak sense of direction (WSD) if there is a function
f
that satisfies the condition that for any node
u
and for any two label sequences
α
and
α
′
...generated by non-trivial walks on
G
starting at
u
,
f
(
α
)
=
f
(
α
′
)
if and only if the two walks end at the same node. The function
f
is referred to as a
coding function of
λ
. The weak sense of direction number of
G
, WSD
(
G
)
, is the smallest integer
k
so that
G
has a WSD-labeling that uses
k
labels. It is known that WSD
(
G
)
≥
Δ
+
(
G
)
, where
Δ
+
(
G
)
is the maximum outdegree of
G
.
Let us say that a function
τ
:
V
(
G
)
→
V
(
H
)
is an
embedding from
G
onto
H
if
τ
demonstrates that
G
is isomorphic to a subgraph of
H
. We show that there are deep connections between WSD-labelings and graph embeddings. First, we prove that when
f
H
is the coding function that naturally accompanies a Cayley graph
H
and
G
has a node that can reach every other node in the graph, then
G
has a WSD-labeling that has
f
H
as a coding function if and only if
G
can be embedded onto
H
. Additionally, we show that the problem “Given
G
, does
G
have a WSD-labeling that uses a particular coding function
f
?” is NP-complete even when
G
and
f
are fairly simple.
Second, when
D
is a distributive lattice,
H
(
D
)
is its Hasse diagram and
G
(
D
)
is its cover graph, then WSD
(
H
(
D
)
)
=
Δ
+
(
H
(
D
)
)
=
d
∗
, where
d
∗
is the smallest integer
d
so that
H
(
D
)
can be embedded onto the
d
-dimensional mesh. Along the way, we also prove that the isometric dimension of
G
(
D
)
is its diameter, and the lattice dimension of
G
(
D
)
is
Δ
+
(
H
(
D
)
)
. Our WSD-labelings are poset-based, making use of Birkhoff’s characterization of distributive lattices and Dilworth’s theorem for posets.