Poising and connectivity of enhancers upon naïve-to-primed transition in human embryonic stem cells (hESCs)

Enhancers are non-coding DNAelements that play crucial roles in transcriptional control, particularly in development. Patterns of histone modifications at enhancers are commonly used to infer their activity states and, poised enhancers (PEs) in particular display a ’bivalent’ chromatin state: the ’active’ H3K4me1 and the ’repressive’, Polycombassociated H3K27me3. Typically observed in pluripotent stem cells (PSCs), it was shown that PEs are required for gene activation later during differentiation. However, the function of the poised state of enhancers remains largely unknown. To trace the emergence of PEs in early development, I have extensively optimized a recently developed low-cell number Capture Hi-C protocol to perform Poised Enhancer Capture Hi-C (PECHi-C) in PSCs, in time course upon the naïve-to-primed transition, which is known to associate with a major shift in the localisation of Polycomb proteins, from a broader to a highly focal pattern. PECHi-C revealed that the PE-mediated regulatory circuitry undergoes significant reorganization between the two states. In particular, I detected three predominant patterns of PE-mediated interactions: the UP, DOWN and CONSTANT interaction classes. Integrating these results with Cut&Tag data on histone modifications revealed an interplay between the acquisition of the poised state at enhancers and their interaction dynamics whereby, at least in some cases, the acquisition of the bivalent signature occurs in parallel to the acquisition of their contacts. Moreover, the analyses suggested that day 3 of the transition is a pivotal point of the naïve-to-primed transition for the emergence of PEs. Overall, this thesis provided further insights into the emergence of PE-mediated regulatory circuitry during early embryogenesis. The different patterns of PE connectivity suggest the presence of diverse regulatory mechanisms of PEs, further suggesting that PEs might play a role at earlier stages of embryogenesis, by ensuring the correct transition from the ground state of pluripotency to the primed state.Open Acces

Thomas Aquinas on the Apprehension of Being: The Role of Judgement in Light of Thirteenth-Century Semantics

Aquinas’ famous comments in his early Scriptum on the Sentences (In I Sent., d. 38, q. 1, a. 3) regarding the intellect’s apprehension of essence and esse have traditionally been interpreted as grounding Aquinas’ doctrine on the judgment of esse. For Aquinas, it appears, what the intellect apprehends in a simple concept is essence. Since esse, for him, is not an essence, it cannot, on the received view, be the object of conceptualization. Therefore, esse is grasped by the intellect only in judgment. The claim that no genuine concept of esse is possible, however, is inconsistent with Aquinas’ theory of signification. A term’s signification is constituted, at least in part, in its “signing relation” with some “concept” in the mind. If, as on the traditional reading, there is no concept of esse, the term ‘esse’ is left without signification. To respond that the term ‘esse’ signs, not a concept, but the judgment in which esse is apprehended is in direct conflict with Aquinas’ claim elsewhere that no term, including ‘ens’ and ‘esse’, signifies a judgment. I propose an alternative interpretation to In I Sent., d. 38, q. 1, a. 3, one that allows for the possibility of a conceptual apprehension of esse. The alternative reading explains Aquinas’ remarks there in light of the theoretical context of the discussion, in particular the theory of propositions and their objects. I show how and why Aquinas develops a distinctive theory of the object of the proposition, that it is concerned with “the esse of a thing” as a complex. Although this complex includes the simple act of being, as for the traditional position (contrary to its major critics), it cannot be reduced to anything simple. Despite the Sentences’ affirmation of a real distinction between a thing’s esse and essence, to which correspond two different operations of the intellect, it does not follow that the human intellect cannot conceive esse, just as it conceives essences, in a simple conception

Tomás de Aquino sobre la aprehensión del ser: el papel del juicio a la luz de la semántica del siglo trece

Demuestra la posibilidad de una simple concepción del ser en la filosofía de Tomás de Aquino. Se demuestra la posibilidad de una aprehensión conceptual del ser a través de una nueva lectura de In I Sent., d. 38, q. 1, a. 3., a la luz del contexto teórico del texto, en particular la teoría de la proposición y sus objetos. La afirmación de una distinción real entre esencia y existencia a la cual se corresponden las dos operaciones del intelecto, no elimina la posibilidad de una simple concepción del ser.Aquinas’ famous comments in his early Scriptum on the Sentences (In I Sent., d. 38, q. 1, a. 3) regarding the intellect’s apprehension of essence and esse have traditionally been interpreted as grounding Aquinas’ doctrine on the judgment of esse. For Aquinas, it appears, what the intellect apprehends in a simple concept is essence. Since esse, for him, is not an essence, it cannot, on the received view, be the object of conceptualization. Therefore, esse is grasped by the intellect only in judgment. The claim that no genuine concept of esse is possible, however, is inconsistent with Aquinas’ theory of signification. A term’s signification is constituted, at least in part, in its “signing relation” with some “concept” in the mind. If, as on the traditional reading, there is no concept of esse, the term ‘esse’ is left without signification. To respond that the term ‘esse’ signs, not a concept, but the judgment in which esse is apprehended is in direct conflict with Aquinas’ claim elsewhere that no term, including ‘ens’ and ‘esse’, signifies a judgment. I propose an alternative interpretation to In I Sent., d. 38, q. 1, a. 3, one that allows for the possibility of a conceptual apprehension of esse. The alternative reading explains Aquinas’ remarks there in light of the theoretical context of the discussion, in particular the theory of propositions and their objects. I show how and why Aquinas develops a distinctive theory of the object of the proposition, that it is concerned with “the esse of a thing” as a complex. Although this complex includes the simple act of being, as for the traditional position (contrary to its major critics), it cannot be reduced to anything simple. Despite the Sentences’ affirmation of a real distinction between a thing’s esse and essence, to which correspond two different operations of the intellect, it does not follow that the human intellect cannot conceive esse, just as it conceives essences, in a simple conception.Tesi

Polar Diels-Alder Reactions using Heterocycles as Electrophiles. Influence of Microwave Irradiation

In this work we studied a series of polar Diels-Alder reactions using different heterocycles derivatives acting as electrophiles joint to dienes of different nucleophilicity, analyzing the effect of the microwave irradiation in these processes. We employ the technique in two conditions: benzene as solvent and solvent free reactions. The last one presents the better yield in shorter time of reaction. Using microwave heating the aromatic cycloadducts are clearly predominant. It is possible to demonstrate that the microwave irradiation has a better influence on these cycloaddition reactions respect to those developed in thermal classical conditions.Fil: Kneeteman, Maria Nelida. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: López Baena, Anna Francesca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química; ArgentinaFil: Della Rosa, Claudia Daniela. Universidad Nacional del Litoral. Facultad de Ingeniería Química; ArgentinaFil: Mancini, Pedro Maximo Emilio. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentin

Clinical Case Studies in Psychoanalytic and Psychodynamic Treatment

This manuscript provides a review of the clinical case study within the field of psychoanalytic and psychodynamic treatment. The method has been contested for methodological reasons and because it would contribute to theoretical pluralism in the field. We summarize how the case study method is being applied in different schools of psychoanalysis, and we clarify the unique strengths of this method and areas for improvement. Finally, based on the literature and on our own experience with case study research, we come to formulate nine guidelines for future case study authors: (1) basic information to include, (2) clarification of the motivation to select a particular patient, (3) information about informed consent and disguise, (4) patient background and context of referral or self-referral, (5) patient's narrative, therapist's observations and interpretations, (6) interpretative heuristics, (7) reflexivity and counter-transference, (8) leaving room for interpretation, and (9) answering the research question, and comparison with other cases

Sustaining the Spindle Assembly Checkpoint to improve cancer therapy

To prevent chromosome segregation errors, the spindle assembly checkpoint (SAC) delays mitosis exit until proper spindle assembly. We found that the FCP1 phosphatase and its downstream target WEE1 kinase oppose the SAC, promoting mitosis exit despite malformed spindles. We further showed that targeting this pathway might be useful for cancer therapy

Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword

Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy

RESORT DAN WEDDING VENUE DI PULAU SAMOSIR SUMATERA

Resort dapat didefinisikan sebagai penginapan yang terletak di kawasan wisata dan menyediakan fasilitas untuk berlibur, rekreasi dan olahraga. Umumnya diperuntukkan bagi tamu yang ingin beristirahat pada hari-hari libur untuk long-stay atau yang sedang datang untuk berekreasi dan menginginkan perubahan dari kegiatan sehari-hari dan terletak cukup jauh dari pusat kota. Sehingga penginapan diharapkan mampu menyediakan fasilitas berlibur, memberi rasa nyaman dan keluar dari rutinitas, memanfaatkan potensi alam yang ada juga mampu menunjukkan budaya atau ciri khas daerah itu sendiri. Terkhusus untuk di Pulau Samoisir area pesisir Danau Toba, pembangunan diharuskan mengacu pada budaya setempat. Pernikahan adalah upacara pengikatan janji nikah yang dirayakan atau dilaksanakan oleh dua orang dengan maksud mensahkan suatu ikatan. Berdasarkan Undang-Undang Republik Indonesia Nomor 1/1974, Bab 1, Pasal 1, perkawinan ialah ikatan lahir batin antara seorang pria dengan seorang wanita sebagai suami istri dengan tujuan membentuk keluarga yang bahagia dan kekal berdasarkan Ketuhanan Yang Maha Esa. Dalam prakteknya, pernikahan di semua kebudayaan cenderung menunjukkan suatu peristiwa saat sepasang calon suami-istri dipertemukan secara formal dihadapan ketua agama, para saksi dan sejumlah hadirin untuk disahkan secara resmi dengan upacara dan ritual-ritual tertentu. Pernikahan dianggap sah apabila dilakukan menurut perundang-undangan yang berlaku dan hukum pernikahan masing-masing agama. Pengesahan secara hukum suatu pernikahan terjadi pada saat dokumen tertulis yang mencatatkan pernikahan ditandatangani. Upacara pernikahan biasanya dilangsungkan sesuai upacara adat yang disepakati dan dirayakan bersama keluarga, teman dan kerabat. Setelah upacara pernikahan selesai, kemudian mereka dinamakan suami istri. Dengan alasan praktis dan privasi, biasanya di dalam satu lokasi dibutuhkan fasilitas yang menunjang upacara pernikahan seperti tempat melakukan foto prawedding, penyewaan baju, ruang rias, upacara pengantin, resepsi, bulan madu dan penginapan keluarga. Pasangan di Indonesia kerapkali memilih Bali sebagai lokasi pernikahan karena di sana sudah tersedia tempat yang menyediakan fasilitas untuk upacara pernikahan di ruang terbuka atau ruang tertutup. Dengan potensi yang tidak jauh berbeda, Pulau Samosir dapat dijadikan pilihan tempat untuk melangsungkan upacara pernikahan baik resepsi maupun tradisional