An optimized IL-12-Fc expands its therapeutic window, achieving strong activity against mouse tumors at tolerable drug doses.

Background: Interleukin-12 (IL-12) has emerged as one of the most potent cytokines for tumor immunotherapy due to its ability to induce interferon γ (IFNγ) and polarize Th1 responses. Clinical use of IL-12 has been limited by a short half-life and narrow therapeutic index.

Methods: We generated a monovalent, half-life-extended IL-12-Fc fusion protein, mDF6006, engineered to retain the high potency of native IL-12 while significantly expanding its therapeutic window.

Importance of cardiac imaging assessment of epicardial adipose tissue after a first episode of myocardial infarction.

Background: Over the past years, information about the crosstalk between the epicardial adipose tissue (EAT) and the cardiovascular system has emerged. Notably, in the context of acute myocardial infarction (AMI), EAT might have a potential role in the pathophysiology of ventricular structural changes and function, and the clinical evolution of patients. This study aims to assess the impact of EAT on morpho-functional changes in the left ventricle (LV) and the outcome of patients after an AMI.

T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a cell surface receptor, is expressed on normal epithelial tissue and highly expressed in cancers of high unmet medical need, such as non-small cell lung, pancreatic, and colorectal cancer. CEACAM receptors undergo homo- and heterophilic interactions thereby regulating normal tissue homeostasis and angiogenesis, and in cancer, tumor invasion and metastasis. CEACAM6 expression on malignant plasma cells inhibits antitumor activity of T cells, and we hypothesize a similar function on epithelial cancer cells.

Bilateral acute angle closure after venlafaxine intake in a young patient with a narrow iridocorneal angle.

We report a case of bilateral and acute angle closure after a single dose of antidepressant venlafaxine in a 40-year-old woman with no previous pathologies, who asked for consultation for blurred vision and pain in the left eye. Initial evaluation included visual acuity, slit lamp biomicroscopy and intraocular pressure (IOP) measurement using Goldmann's applanation tonometer. Gonioscopy and fundus examination were also performed in both eyes.

The role of syllables in sign language production.

The aim of the present study was to investigate the functional role of syllables in sign language and how the different phonological combinations influence sign production. Moreover, the influence of age of acquisition was evaluated. Deaf signers (native and non-native) of Catalan Signed Language (LSC) were asked in a picture-sign interference task to sign picture names while ignoring distractor-signs with which they shared two phonological parameters (out of three of the main sign parameters: Location, Movement, and Handshape).

Lexical access in American Sign Language: an ERP investigation of effects of semantics and phonology.

That language forms (phonology) are arbitrarily related to their meanings (semantics) is often considered a basic property of human languages. Naturally occurring sign languages, however, often appear to conflate form and meaning. In this paper we examine whether this close coupling has processing consequences for lexical access.

Electrophysiological evidence for phonological priming in Spanish Sign Language lexical access.

Interactive activation models of lexical access assume that the presentation of a given word activates not only its lexical representation but also those corresponding to words similar in form. Current theories are based on data from oral and written languages, and therefore signed languages represent a special challenge for existing theories of word recognition and lexical access since they allow us to question what the genuine fundamentals of human language are and what might be modality-specific adaptation. The aim of the present study is to determine the electrophysiological correlates and time course of phonological processing of Spanish Sign Language (LSE).

Dissociating linguistic and non-linguistic gesture processing: electrophysiological evidence from American Sign Language.

A fundamental advance in our understanding of human language would come from a detailed account of how non-linguistic and linguistic manual actions are differentiated in real time by language users. To explore this issue, we targeted the N400, an ERP component known to be sensitive to semantic context. Deaf signers saw 120 American Sign Language sentences, each consisting of a "frame" (a sentence without the last word; e.

2D ultrafast HMBC: a valuable tool for monitoring organic reactions.

Ultrafast 2D HMBC spectroscopy permits real-time monitoring of a reaction based on the structural changes produced in a carbonyl carbon atom. This new technique was used to study the reaction of ketones, nitriles, and Tf(2)O, affording relevant information about new intermediates and kinetic data.

Neural correlates of visual working memory: fMRI amplitude predicts task performance.

We used fMRI to investigate how moment-to-moment neural activity contributes to success or failure on individual trials of a visual working memory (WM) task. We found that different nodes of a distributed cortical network were activated to a greater extent for correct compared to incorrect trials during stimulus encoding, memory maintenance during delays, and at test. A logistic regression analysis revealed that the fMRI signal amplitude during the delay interval in a network of frontoparietal regions predicted successful performance on a trial-by-trial basis.