Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex<sup>GM-CSF</sup>]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions

Low-gravity solidification of cast iron and space technology applications

Two types of analyses relating to cast iron solidification were conducted. A theoretical analysis using a computer to predict the cooling versus time relationship throughout the test specimen was performed. Tests were also conducted in a ground-based laboratory to generate a cooling time curve for cast iron. In addition, cast iron was cooled through the solidification period on a KC-135 and an F-104 aircraft while these aircraft were going through a period of low gravity. Future subjects for low gravity tests are enumerated

Non-commutative crepant resolutions: scenes from categorical geometry

Non-commutative crepant resolutions are algebraic objects defined by Van den Bergh to realize an equivalence of derived categories in birational geometry. They are motivated by tilting theory, the McKay correspondence, and the minimal model program, and have applications to string theory and representation theory. In this expository article I situate Van den Bergh's definition within these contexts and describe some of the current research in the area.Comment: 57 pages; final version, to appear in "Progress in Commutative Algebra: Ring Theory, Homology, and Decompositions" (Sean Sather-Wagstaff, Christopher Francisco, Lee Klingler, and Janet Vassilev, eds.), De Gruyter. Incorporates many small bugfixes and adjustments addressing comments from the referee and other

Recognising the ageing face: the role of age in face processing

The effects of age-induced changes on face recognition were investigated as a means of exploring the role of age in the encoding of new facial memories. The ability of participants to recognise each of six previously learnt faces was tested with versions which were either identical to the learnt faces, the same age (but different in pose and expression), or younger or older in age. Participants were able to cope well with facial changes induced by ageing: their performance with older, but not younger, versions was comparable to that with faces which differed only in pose and expression. Since the large majority of different age versions were recognised successfully, it can be concluded that the process of recognition does not require an exact match in age characteristics between the stored representation of a face and the face currently in view. As the age-related changes explored here were those that occur during the period of growth, this in turn implies that the underlying structural physical properties of the face are (in addition to pose and facial expression) invariant to a certain extent

On the growth of the Betti sequence of the canonical module

We study the growth of the Betti sequence of the canonical module of a Cohen-Macaulay local ring. It is an open question whether this sequence grows exponentially whenever the ring is not Gorenstein. We answer the question of exponential growth affirmatively for a large class of rings, and prove that the growth is in general not extremal. As an application of growth, we give criteria for a Cohen-Macaulay ring possessing a canonical module to be Gorenstein.Comment: 12 pages. version 2: includes omitted author contact informatio

Factors influencing the accuracy of age-estimates of unfamiliar faces

Factors affecting the accuracy with which adults could assess the age of unfamiliar male faces aged between 5 and 70 years were examined. In the first experiment twenty-five 'young' adult subjects, aged 16-25, and twenty-five 'old' adults, aged 51-60, were used. Each subject saw five versions of three different faces: these consisted of an original version of each face and four manipulated versions of it. The manipulations consisted of mirror reversal, pseudo-cardioidal strain, thresholding, and elimination of all but the internal features of the face. The second experiment was similar except that a between-subjects design was used: each subject saw three faces for each age category of target face, but was exposed to only a single type of manipulation (plus a set of 'original' faces which were identical for all groups, so that the comparability of the different groups in age estimation could be checked). Results from both experiments were similar. Age estimates for unmanipulated 'original' faces were highly accurate, although subjects were most accurate with target faces that were within their own age range. Results for the manipulated faces implied that the importance of cardioidal strain as a necessary and sufficient cue to age may have been overestimated in previous reports: subjects' age estimates were accurate when cardioidal strain was absent from the stimulus, and poor when cardioidal strain was the only cue available