In and Out of SSA : a Denotational Specification

International audienceWe present non-standard denotational specifications of the SSA form and of its conversion processes from and to imperative programming languages. Thus, we provide a strong mathematical foundation for this intermediate code representation language used in modern compilers such as GCC or Intel CC. More specifically, we provide (1) a new functional approach to SSA, the Static Single Assignment form, together with its denotational semantics, (2) a collecting denotational semantics for a simple imperative language Imp, (3) a non-standard denotational semantics specifying the conversion of Imp to SSA and (4) a non-standard denotational semantics for the reverse SSA to Imp conversion process. These translations are proven correct, ensuring that the structure of the memory states manipulated by imperative constructs is preserved in compilers' middle ends that use the SSA form as control-flow data representation. Interestingly, a s unexpected by-products of our conversion procedures, we offer (1) a new proof of the reducibility of the RAM computing model to the domain of Kleene's partial recursive functions, to which SSA is strongly related, and, on a more practical note, (2) a new algorithm to perform program slicing in imperative programming languages. All these specifications have been prototyped using GNU Common Lisp. These fundamental results prove that the widely used SSA technology is sound. Our formal denotational framework further suggests that the SSA form could become a target of choice for other optimization analysis techniques such as abstract interpretation or partial evaluation. Indeed, since the SSA form is language-independent, the resulting optimizations would be automatically enabled for any source language supported by compilers such as GCC

Management options in the sudden hearing loss of a diabetic patient

The aim of our paper is to highlight the main therapeutic principles and the management options in the case of a diabetic patient who has had a sudden hearing loss. Mainly, the aim is to underline the sudden hearing loss treatment adjustment of the diabetic patient compared to the non-diabetic patient. By understanding the mechanism of sudden hearing loss in a diabetic patient, namely the impact of glycemic variations and their implication on the microvascular structures of the inner ear, we try to underline the treatment principles and management options of the previously mentioned combined pathologies. Thus, it is necessary to adapt the classes of drugs used in the case of sudden sensorineural hearing loss of the diabetic patient in comparison with the non-diabetic patient, in order not to aggravate or complicate the patient’s functional status. Therefore, the treatment will need to be adapted both by classes of medication and by the type of administration used. Adequate control of the progression, treatment and complications of diabetes mellitus ensures optimal treatment management in case of a sudden hearing loss and therefore interferes with the favorable functional hearing outcomes. The role of this paper is not only to state the therapeutic principles in the case of sudden hearing loss in a diabetic patient, but also to analyze the impact on the management of potential local and systemic risk factors

Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling

BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D) and invasion of three-dimensional (3D) collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. RESULTS: LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (~700 μm over 48 hours) in response to either lipid. siRNA targeting of LPA(1 )and Rac1, or S1P(1), Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (~125 μm vs. ~45 μm) and velocity of invasion (~0.09 μm/min vs. ~0.03 μm/min) only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs)-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT)-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in this process. CONCLUSION: LPA is a fundamental regulator of MT1-MMP-dependent tumor cell invasion of 3D collagen matrices. In contrast, S1P appears to act as an inhibitory stimulus in most cases, while stimulating only select tumor lines. MT1-MMP is required only when tumor cells navigate 3D barriers and not when cells migrate on 2D substrata. We demonstrate that tumor cells require coordinate regulation of LPA/S1P receptors and Rho GTPases to migrate, and additionally, require MT1-MMP in order to invade collagen matrices during neoplastic progression

Neuroendocrine carcinoma of the breast: a case report

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence and prognosis remain controversial in the literature. Regarding the presentation, there are no differences from other breast carcinomas and clinical syndromes related to hormone production are extremely rare. Refinement of the classification of neuroendocrine neoplasms of the breast is needed in order to improve the reproducibility of their diagnostic criteria and to define their clinical significance. This article presents the case of a 44-year-old female patient diagnosed with invasive breast carcinoma with neuroendocrine features, according to the 2012 World Health Organization (WHO) definition, with focus on presentation, clinical manifestations, diagnostic approach and differential diagnosis