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The pH (low) insertion peptides (pHLIPs) target acidity at the surfaces of cancer cells and show utility in a wide range of applications, including tumor imaging and intracellular delivery of therapeutic agents. Here we report pHLIP constructs that significantly improve the targeted delivery of agents into tumor cells. The investigated constructs include pHLIP bundles (conjugates consisting of two or four pHLIP peptides linked by polyethylene glycol) and Var3 pHLIPs containing either the nonstandard amino acid, γ-carboxyglutamic acid, or a glycine−leucine−leucine motif. The performance of the constructs in vitro and in vivo was compared with previous pHLIP variants. A wide range of experiments was performed on nine constructs including (i) biophysical measurements using steady-state and kinetic fluorescence, circular dichroism, and oriented circular dichroism to study the pH-dependent insertion of pHLIP variants across the membrane lipid bilayer; (ii) cell viability assays to gauge the pH-dependent potency of peptide-toxin constructs by assessing the intracellular delivery of the polar, cell-impermeable cargo molecule amanitin at physiological and low pH (pH 7.4 and 6.0, respectively); and (iii) tumor targeting and biodistribution measurements using fluorophore-peptide conjugates in a breast cancer mouse model. The main principles of the design of pHLIP variants for a range of medical applications are discussed.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

Fluorescence imaging has seen enduring use in blood flow visualization and is now finding a new range of applications in image-guided surgery. In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a surgical fluorescent dye used widely for imaging blood flow. We studied pHLIP ICG interaction with the cell membrane lipid bilayer, the pharmacology and toxicology in vitro and in vivo (mice and dogs), and the biodistribution and clearance of pHLIP ICG in mice. The pHLIP ICG tumor targeting and imaging efficacy studies were carried out in several murine and human mouse tumor models. Blood vessels were imaged in mice and pigs. Clinical Stryker imaging instruments for endoscopy and open surgery were used in the study. Intravenously administered pHLIP ICG exhibits a multi-hour circulation half-life, offering protracted delineation of vasculature. As it clears from the blood, pHLIP ICG targets tumors and tumor stroma, marking them for surgical removal. pHLIP ICG is non-toxic, marks blood flow for hours after injection, and effectively delineates tumors for improved resection on the day after administration.

This paper explores the different factors that appear to affect the on-going construction of second language authorial identity in a professional academic environment in Mexico. Through narrative research methodology from a qualitative paradigm, the everyday struggles of two university professors to maintain their professional status in second language writing are explored. The areas of study for these two are chemistry and penal law. With data the learning processes of entering into a community of second language writers are studied as well as the problems they faced and how they resolved them. Finally, the process of negotiating an authorial identity in a second language seems to be a constant underlying struggle composed of a variety of psychological factors.

International collaborative research often refers to collaboration among the researchers and the participants. Few studies investigate the collaborative process among the researchers themselves. Assumptions about the qualitative research process, institutional requirements, and even epistemological orientations, are pervasive. Our experience conducting an empirical research study as a collaborative effort amongst a research team in Mexico and the United States challenged and transformed our assumptions about collaborative qualitative research in terms of organizational compatibility: (a) understanding research perspective and themes, (b) interpreting rules and regulations (c) physical travel between countries, and (d) how research products are counted. We address each assumption through a dialogue, including how our collaborative research diverged from the assumption and how this divergence has impacted our own practice.

This paper explores the construction of identity in an academic learning environment in Central Mexico, and shows how identity may be linked to non-language factors such as emotions or family. These issues are associated with elements of hybrid identity. To analyze this we draw on language choice as a tool used for the construction of identity and for showcasing and defending identity through exploratory interviews with the bilingual students and teachers. The results draw our attention towards the role of non-linguistic variables and their relationship to emotional and contextual issues that influence how academic writing occurs within the school confines, where hybrid identities may be constructed for academic purposes.

The present study explores the use of the first language in a context of foreign language teaching. This qualitative research presents the classroom practice and points of view of French and English teachers and students within a public educational institute in central Mexico using the techniques of questionnaires and semi-structured interviews. The results show that teachers and the majority of students perceive the use of the first language as positive and part of the teaching and learning process. A small number of students do not like the use of the first language in the classroom and prefer that their teachers use the target language only. La presente investigación explora el uso de la lengua materna en un contexto de enseñanza de lenguas extranjeras. Esta investigación cualitativa presenta la práctica docente y los puntos de vista de maestros y alumnos de francés e inglés en el contexto de una universidad pública del centro de México, mediante el uso de las técnicas del cuestionario y la entrevista semiestructurada. Los resultados muestran que tanto los maestros como la mayoría de los alumnos perciben el uso de la lengua materna como algo positivo en el proceso de enseñanza-aprendizaje. Un número reducido de estudiantes rechaza el uso de la lengua materna y prefiere que su clase de lengua extranjera sea dirigida exclusivamente en la lengua meta.

In this article, we attempt to conciliate the issues of an audit culture that surround the postgraduate programs in Mexico through the National Council of Science and Technology (CONACyT) with highly flexible definition of the course using duoethnography. The goal being to satisfy national requirements yet retain freedom in applied research in English as a foreign language teaching. This is done through an intense process of data recycling with the student participants in a semester-long analysis. This analysis also involved a continuous editing and reediting process to try and connect all the participants’ autobiographical dots of the course to arrive at a definition.

In this article, we attempt to conciliate the issues of an audit culture that surround the postgraduate programs in Mexico through the National Council of Science and Technology (CONACyT) with highly flexible definition of the course using duoethnography. The goal being to satisfy national requirements yet retain freedom in applied research in English as a foreign language teaching This is done through an intense process of data recycling with the student participants in a semester-long analysis. This analysis also involved a continuous editing and reediting process to try and connect all the participants' autobiographical dots of the course to arrive at a definition. Keywords: Audit Culture, CONACyT, Duoethnography, Evaluation, Professional Practicum

After heart disease, cancer is the leading cause of death in the U.S. According to the National Cancer Institute, approximately 38% of the population will be diagnosed with cancer at some point over the course of their life. This number is only expected to increase with the increased age of the general public due to medical progress, leading to an increased importance in finding effective and convenient treatment that can be used across a wide array of cancers. In theory, any tumor can be destroyed using enough of a cytotoxic method, whether it be heating, radiation, surgery, or chemotherapy. However, because cancer cells are derived from a person’s own healthy cells mutating, all of these treatments involve destroying healthy tissue in the process. Because of this, the most important aspect of any treatment modality is its tumor specificity: the ability of the treatment to target cancerous tissue vs. healthy tissue. The higher the ratio of cancer cell death to healthy cell death a treatment contains, the more effectively it can be used in clinical practice. A common method of targeting cancerous tissues is by targeting biomarkers that are overexpressed in cancer cells. These can include utilizing antibody, receptor, or vitamin bindings. While these methods can increase the specificity of treatment, there are also associated shortcomings with them. They tend to be cell-line specific, so a treatment that may work for one strain of cancer may not have the desired effect across other lines. Even within a single cancer strain, there exists heterogeneity a tumor, resulting in some cells not expressing the biomarkers to the extent needed for adequate targeting. This not only results in some cells surviving damage, but those cells then go on to reproduce, passing on their traits, and causing the tumor to adapt to become more resistant to that treatment. Within this arises the need to target a more general biomarker presented throughout all cancer cells and strains. In 1931, the Nobel Prize in Physiology was awarded to Dr. Otto Heinrich Warburg for his discovery of what is known as the Warburg effect. In his research, Dr. Warburg discovered that even in the presence of oxygen, cancerous tissue produces the majority of its energy via anaerobic glycolysis instead of the aerobic oxidative phosphorylation. Glycolysis is a much less efficient, but faster, process, resulting in an excess of positively charged hydrogen ion byproducts. These are pumped outside of the cell membrane to maintain a normal pH within the cell, which results in a low pH environment immediately extracellularly to cancerous tissue. This acidity at the surface of cancer cells is ubiquitous across solid tumors, making it an ideal biomarker to target for cancer treatment. pH-Low Insertion Peptide (pHLIP) is a pH-dependent peptide, whose pH-dependent action is based on the protonation of the aspartic (Asp) and glutamic (Glu) acid residues at tge C-terminal end of the peptide. In the presence of a low pH environment, the normally negatively charged Asp and Glu residues of pHLIP become protonated, increasing the overall hydrophobicity of the polypeptide. In the presence of a lipid bilayer, it triggers the insertion of the peptide across the bilayer to form a transmembrane alpha helix. Because of the Warburg effect described above, the acidity surrounding a cancerous tissue therefor promotes selective insertion of pHLIP across the cell membrane of tumor cells. As a result, different cargoes can be attached to the peptide, consequently being either tethered or translocated across membrane of cells in acidic diseased tissue at much higher proportions than in healthy tissue. The main goal of this work was to evaluate the efficacy of different pHLIP variants to target tumors and deliver cargo across the membrane for therapeutic and diagnostic/imaging applications. In therapeutic applications, the attached cargo would directly induce cell death via external radiation enhancement, cell heating, or radioactive emission. For this, gold nanoparticles (GNPs) were studied, as gold is an inert and biocompatible. The focus of this work was to create GNPs coated with pHLIP to allow for enhancement of radiation via Auger electron emission, and to explore the possibility of creating gold-coated bicelles for heating via plasmon resonance. For diagnostic and imaging applications, the attached cargo would be used to visually differentiate the cancerous and healthy tissue, and be used in coordination with therapeutic strategies such as surgery for treatment. For this, the near-infrared dye indocyanine green (ICG) was conjugated to pHLIP to make ICG-pHLIP. ICG is already used in clinics for fluorescence guided surgery for imaging of lymph nodes and blood flow, making ICG-pHLIPs transition to clinics more straightforward and efficient. The focus of this study was to find the ICG-pHLIPs selectivity to cancerous tissue in vivo in balb-c and nude mice, exploring proof of concept for its continuation into human trials.