Stable Crystalline Salts of Haloperidol: A Highly Water-Soluble Mesylate Salt

Haloperidol, an antipsychotic drug, was screened for new solid crystalline phases using high throughput crystallization in pursuit of solubility improvement. Due to the highly basic nature of the API, all the solid forms with acids were obtained in the form of salts. Eleven crystalline salts in the form of oxalate (1:1), benzoate (1:1), salicylate (1:1 and 1:2), 4-hydroxybenzoate (1:1), 4-hydroxybenzoate ethyl acetate solvate (1:1:1), 3,4-dihydroxybenzoate (1:1), 3,5-dihydroxybenzoate (1:1), mesylate (1:1), besylate (1:1), and tosylate (1:1) salt were achieved. There is an insertion of carboxylate or sulfonate anion into the hydrogen bonding pattern of haloperidol. The salts with the aliphatic carboxylic acids were found to be more prone to form salt hydrates compared with aromatic carboxylate salts. All the salts were subjected to solubility measurement in water at neutral pH. There was no direct correlation observed between the solubility of the salt and its coformer. All the salts are stable at room temperature as well as after 24 h slurry experiment except the oxalate salt, which showed an unusual phase transformation from its hydrated form to the anhydrous form. A structureproperty relationship was examined to analyze the solubility behavior of the solid forms.

Discovering Math APIs by Mining Unit Tests

In today's API-rich world, programmer productivity depends heavily on the programmer's ability to discover the required APIs. In this paper, we present a technique and tool, called MATHFINDER, to discover APIs for mathematical computations by mining unit tests of API methods. Given a math expression, MATHFINDER synthesizes pseudo-code to compute the expression by mapping its subexpressions to API method calls. For each subexpression, MATHFINDER searches for a method such that there is a mapping between method inputs and variables of the subexpression. The subexpression, when evaluated on the test inputs of the method under this mapping, should produce results that match the method output on a large number of tests. We implemented MATHFINDER as an Eclipse plugin for discovery of third-party Java APIs and performed a user study to evaluate its effectiveness. In the study, the use of MATHFINDER resulted in a 2x improvement in programmer productivity. In 96% of the subexpressions queried for in the study, MATHFINDER retrieved the desired API methods as the top-most result. The top-most pseudo-code snippet to implement the entire expression was correct in 93% of the cases. Since the number of methods and unit tests to mine could be large in practice, we also implement MATHFINDER in a MapReduce framework and evaluate its scalability and response time.

On the Parameterized Complexity of the Maximum Edge 2-Coloring Problem

We investigate the parameterized complexity of the following edge coloring problem motivated by the problem of channel assignment in wireless networks. For an integer q >= 2 and a graph G, the goal is to find a coloring of the edges of G with the maximum number of colors such that every vertex of the graph sees at most q colors. This problem is NP-hard for q >= 2, and has been well-studied from the point of view of approximation. Our main focus is the case when q = 2, which is already theoretically intricate and practically relevant. We show fixed-parameter tractable algorithms for both the standard and the dual parameter, and for the latter problem, the result is based on a linear vertex kernel.

Subexponential Algorithm for d-Cluster Edge Deletion: Exception or Rule?

The correlation clustering problem is a fundamental problem in both theory and practice, and it involves identifying clusters of objects in a data set based on their similarity. A traditional modeling of this question as a graph theoretic problem involves associating vertices with data points and indicating similarity by adjacency. Clusters then correspond to cliques in the graph. The resulting optimization problem, Cluster Editing (and several variants) are very well-studied algorithmically. In many situations, however, translating clusters to cliques can be somewhat restrictive. A more flexible notion would be that of a structure where the vertices are mutually ``not too far apart'', without necessarily being adjacent. One such generalization is realized by structures called s-clubs, which are graphs of diameter at most s. In this work, we study the question of finding a set of at most k edges whose removal leaves us with a graph whose components are s-clubs. Recently, it has been shown that unless Exponential Time Hypothesis fail (ETH) fails Cluster Editing (whose components are 1-clubs) does not admit sub-exponential time algorithm STACS, 2013]. That is, there is no algorithm solving the problem in time 2 degrees((k))n(O(1)). However, surprisingly they show that when the number of cliques in the output graph is restricted to d, then the problem can be solved in time O(2(O(root dk)) + m + n). We show that this sub-exponential time algorithm for the fixed number of cliques is rather an exception than a rule. Our first result shows that assuming the ETH, there is no algorithm solving the s-Club Cluster Edge Deletion problem in time 2 degrees((k))n(O(1)). We show, further, that even the problem of deleting edges to obtain a graph with d s-clubs cannot be solved in time 2 degrees((k))n(O)(1) for any fixed s, d >= 2. This is a radical contrast from the situation established for cliques, where sub-exponential algorithms are known.

A constant factor approximation algorithm for boxicity of circular arc graphs

The boxicity (resp. cubicity) of a graph G(V, E) is the minimum integer k such that G can be represented as the intersection graph of axis parallel boxes (resp. cubes) in R-k. Equivalently, it is the minimum number of interval graphs (resp. unit interval graphs) on the vertex set V, such that the intersection of their edge sets is E. The problem of computing boxicity (resp. cubicity) is known to be inapproximable, even for restricted graph classes like bipartite, co-bipartite and split graphs, within an O(n(1-epsilon))-factor for any epsilon > 0 in polynomial time, unless NP = ZPP. For any well known graph class of unbounded boxicity, there is no known approximation algorithm that gives n(1-epsilon)-factor approximation algorithm for computing boxicity in polynomial time, for any epsilon > 0. In this paper, we consider the problem of approximating the boxicity (cubicity) of circular arc graphs intersection graphs of arcs of a circle. Circular arc graphs are known to have unbounded boxicity, which could be as large as Omega(n). We give a (2 + 1/k) -factor (resp. (2 + log n]/k)-factor) polynomial time approximation algorithm for computing the boxicity (resp. cubicity) of any circular arc graph, where k >= 1 is the value of the optimum solution. For normal circular arc (NCA) graphs, with an NCA model given, this can be improved to an additive two approximation algorithm. The time complexity of the algorithms to approximately compute the boxicity (resp. cubicity) is O(mn + n(2)) in both these cases, and in O(mn + kn(2)) = O(n(3)) time we also get their corresponding box (resp. cube) representations, where n is the number of vertices of the graph and m is its number of edges. Our additive two approximation algorithm directly works for any proper circular arc graph, since their NCA models can be computed in polynomial time. (C) 2014 Elsevier B.V. All rights reserved.

Fixed-orientation equilateral triangle matching of point sets

Given a point set P and a class C of geometric objects, G(C)(P) is a geometric graph with vertex set P such that any two vertices p and q are adjacent if and only if there is some C is an element of C containing both p and q but no other points from P. We study G(del)(P) graphs where del is the class of downward equilateral triangles (i.e., equilateral triangles with one of their sides parallel to the x-axis and the corner opposite to this side below that side). For point sets in general position, these graphs have been shown to be equivalent to half-Theta(6) graphs and TD-Delaunay graphs. The main result in our paper is that for point sets P in general position, G(del)(P) always contains a matching of size at least vertical bar P vertical bar-1/3] and this bound is tight. We also give some structural properties of G(star)(P) graphs, where is the class which contains both upward and downward equilateral triangles. We show that for point sets in general position, the block cut point graph of G(star)(P) is simply a path. Through the equivalence of G(star)(P) graphs with Theta(6) graphs, we also derive that any Theta(6) graph can have at most 5n-11 edges, for point sets in general position. (C) 2013 Elsevier B.V. All rights reserved.

2-Connecting outerplanar graphs without blowing up the pathwidth

Given a connected outerplanar graph G of pathwidth p, we give an algorithm to add edges to G to get a supergraph of G, which is 2-vertex-connected, outerplanar and of pathwidth O(p). This settles an open problem raised by Biedl 1], in the context of computing minimum height planar straight line drawings of outerplanar graphs, with their vertices placed on a two-dimensional grid. In conjunction with the result of this paper, the constant factor approximation algorithm for this problem obtained by Biedl 1] for 2-vertex-connected outerplanar graphs will work for all outer planar graphs. (C) 2014 Elsevier B.V. All rights reserved.

Parameterized Algorithms for MAX COLORABLE INDUCED SUBGRAPH Problem on Perfect Graphs

We address the parameterized complexity ofMaxColorable Induced Subgraph on perfect graphs. The problem asks for a maximum sized q-colorable induced subgraph of an input graph G. Yannakakis and Gavril IPL 1987] showed that this problem is NP-complete even on split graphs if q is part of input, but gave a n(O(q)) algorithm on chordal graphs. We first observe that the problem is W2]-hard parameterized by q, even on split graphs. However, when parameterized by l, the number of vertices in the solution, we give two fixed-parameter tractable algorithms. The first algorithm runs in time 5.44(l) (n+#alpha(G))(O(1)) where #alpha(G) is the number of maximal independent sets of the input graph. The second algorithm runs in time q(l+o()l())n(O(1))T(alpha) where T-alpha is the time required to find a maximum independent set in any induced subgraph of G. The first algorithm is efficient when the input graph contains only polynomially many maximal independent sets; for example split graphs and co-chordal graphs. The running time of the second algorithm is FPT in l alone (whenever T-alpha is a polynomial in n), since q <= l for all non-trivial situations. Finally, we show that (under standard complexitytheoretic assumptions) the problem does not admit a polynomial kernel on split and perfect graphs in the following sense: (a) On split graphs, we do not expect a polynomial kernel if q is a part of the input. (b) On perfect graphs, we do not expect a polynomial kernel even for fixed values of q >= 2.

Vertex Cover Gets Faster and Harder on Low Degree Graphs

The problem of finding an optimal vertex cover in a graph is a classic NP-complete problem, and is a special case of the hitting set question. On the other hand, the hitting set problem, when asked in the context of induced geometric objects, often turns out to be exactly the vertex cover problem on restricted classes of graphs. In this work we explore a particular instance of such a phenomenon. We consider the problem of hitting all axis-parallel slabs induced by a point set P, and show that it is equivalent to the problem of finding a vertex cover on a graph whose edge set is the union of two Hamiltonian Paths. We show the latter problem to be NP-complete, and also give an algorithm to find a vertex cover of size at most k, on graphs of maximum degree four, whose running time is 1.2637(k) n(O(1)).

Mining Unit Tests for Discovery and Migration of Math APIs

Today's programming languages are supported by powerful third-party APIs. For a given application domain, it is common to have many competing APIs that provide similar functionality. Programmer productivity therefore depends heavily on the programmer's ability to discover suitable APIs both during an initial coding phase, as well as during software maintenance. The aim of this work is to support the discovery and migration of math APIs. Math APIs are at the heart of many application domains ranging from machine learning to scientific computations. Our approach, called MATHFINDER, combines executable specifications of mathematical computations with unit tests (operational specifications) of API methods. Given a math expression, MATHFINDER synthesizes pseudo-code comprised of API methods to compute the expression by mining unit tests of the API methods. We present a sequential version of our unit test mining algorithm and also design a more scalable data-parallel version. We perform extensive evaluation of MATHFINDER (1) for API discovery, where math algorithms are to be implemented from scratch and (2) for API migration, where client programs utilizing a math API are to be migrated to another API. We evaluated the precision and recall of MATHFINDER on a diverse collection of math expressions, culled from algorithms used in a wide range of application areas such as control systems and structural dynamics. In a user study to evaluate the productivity gains obtained by using MATHFINDER for API discovery, the programmers who used MATHFINDER finished their programming tasks twice as fast as their counterparts who used the usual techniques like web and code search, IDE code completion, and manual inspection of library documentation. For the problem of API migration, as a case study, we used MATHFINDER to migrate Weka, a popular machine learning library. Overall, our evaluation shows that MATHFINDER is easy to use, provides highly precise results across several math APIs and application domains even with a small number of unit tests per method, and scales to large collections of unit tests.

Using formal reasoning on a model of tasks for FreeRTOS

FreeRTOS is an open-source real-time microkernel that has a wide community of users. We present the formal specification of the behaviour of the task part of FreeRTOS that deals with the creation, management, and scheduling of tasks using priority-based preemption. Our model is written in the Z notation, and we verify its consistency using the Z/Eves theorem prover. This includes a precise statement of the preconditions for all API commands. This task model forms the basis for three dimensions of further work: (a) the modelling of the rest of the behaviour of queues, time, mutex, and interrupts in FreeRTOS; (b) refinement of the models to code to produce a verified implementation; and (c) extension of the behaviour of FreeRTOS to multi-core architectures. We propose all three dimensions as benchmark challenge problems for Hoare's Verified Software Initiative.

GPU-based normalized cuts for road extraction using satellite imagery

This paper presents a GPU implementation of normalized cuts for road extraction problem using panchromatic satellite imagery. The roads have been extracted in three stages namely pre-processing, image segmentation and post-processing. Initially, the image is pre-processed to improve the tolerance by reducing the clutter (that mostly represents the buildings, vegetation,. and fallow regions). The road regions are then extracted using the normalized cuts algorithm. Normalized cuts algorithm is a graph-based partitioning `approach whose focus lies in extracting the global impression (perceptual grouping) of an image rather than local features. For the segmented image, post-processing is carried out using morphological operations - erosion and dilation. Finally, the road extracted image is overlaid on the original image. Here, a GPGPU (General Purpose Graphical Processing Unit) approach has been adopted to implement the same algorithm on the GPU for fast processing. A performance comparison of this proposed GPU implementation of normalized cuts algorithm with the earlier algorithm (CPU implementation) is presented. From the results, we conclude that the computational improvement in terms of time as the size of image increases for the proposed GPU implementation of normalized cuts. Also, a qualitative and quantitative assessment of the segmentation results has been projected.

LOWER BOUNDS FOR BOXICITY

An axis-parallel b-dimensional box is a Cartesian product R-1 x R-2 x ... x R-b where R-i is a closed interval of the form a(i),b(i)] on the real line. For a graph G, its boxicity box(G) is the minimum dimension b, such that G is representable as the intersection graph of boxes in b-dimensional space. Although boxicity was introduced in 1969 and studied extensively, there are no significant results on lower bounds for boxicity. In this paper, we develop two general methods for deriving lower bounds. Applying these methods we give several results, some of which are listed below: 1. The boxicity of a graph on n vertices with no universal vertices and minimum degree delta is at least n/2(n-delta-1). 2. Consider the g(n,p) model of random graphs. Let p <= 1 - 40logn/n(2.) Then with high `` probability, box(G) = Omega(np(1 - p)). On setting p = 1/2 we immediately infer that almost all graphs have boxicity Omega(n). Another consequence of this result is as follows: For any positive constant c < 1, almost all graphs on n vertices and m <= c((n)(2)) edges have boxicity Omega(m/n). 3. Let G be a connected k-regular graph on n vertices. Let lambda be the second largest eigenvalue in absolute value of the adjacency matrix of G. Then, the boxicity of G is a least (kappa(2)/lambda(2)/log(1+kappa(2)/lambda(2))) (n-kappa-1/2n). 4. For any positive constant c 1, almost all balanced bipartite graphs on 2n vertices and m <= cn(2) edges have boxicity Omega(m/n).

On the Communication Complexity of Secret Key Generation in the Multiterminal Source Model

Communication complexity refers to the minimum rate of public communication required for generating a maximal-rate secret key (SK) in the multiterminal source model of Csiszar and Narayan. Tyagi recently characterized this communication complexity for a two-terminal system. We extend the ideas in Tyagi's work to derive a lower bound on communication complexity in the general multiterminal setting. In the important special case of the complete graph pairwise independent network (PIN) model, our bound allows us to determine the exact linear communication complexity, i.e., the communication complexity when the communication and SK are restricted to be linear functions of the randomness available at the terminals.

Analysis of the hierarchical structure of the B. subtilis transcriptional regulatory network

The transcriptional regulation of gene expression is orchestrated by complex networks of interacting genes. Increasing evidence indicates that these `transcriptional regulatory networks' (TRNs) in bacteria have an inherently hierarchical architecture, although the design principles and the specific advantages offered by this type of organization have not yet been fully elucidated. In this study, we focussed on the hierarchical structure of the TRN of the gram-positive bacterium Bacillus subtilis and performed a comparative analysis with the TRN of the gram-negative bacterium Escherichia coli. Using a graph-theoretic approach, we organized the transcription factors (TFs) and sigma-factors in the TRNs of B. subtilis and E. coli into three hierarchical levels (Top, Middle and Bottom) and studied several structural and functional properties across them. In addition to many similarities, we found also specific differences, explaining the majority of them with variations in the distribution of s-factors across the hierarchical levels in the two organisms. We then investigated the control of target metabolic genes by transcriptional regulators to characterize the differential regulation of three distinct metabolic subsystems (catabolism, anabolism and central energy metabolism). These results suggest that the hierarchical architecture that we observed in B. subtilis represents an effective organization of its TRN to achieve flexibility in response to a wide range of diverse stimuli.