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Exploring the next generation of antibody–drug conjugates
Antibody–drug conjugates (ADCs) are a promising cancer treatment modality that enables the selective delivery of highly cytotoxic payloads to tumours. However, realizing the full potential of this platform necessitates innovative molecular designs to tackle several clinical challenges such as drug resistance, tumour heterogeneity and treatment-related adverse effects. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody–drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges. For example, probody–drug conjugates can enhance tumour specificity, whereas bispecific ADCs and dual-drug ADCs can address resistance and heterogeneity with enhanced activity. The incorporation of immune-stimulating and protein-degrader ADCs, which have distinct mechanisms of action, into existing treatment strategies could enable multimodal cancer treatment. Despite the promising outlook, the importance of patient stratification and biomarker identification cannot be overstated for these emerging ADCs, as these factors are crucial to identify patients who are most likely to derive benefit. As we continue to deepen our understanding of tumour biology and refine ADC design, we will edge closer to developing truly effective and safe ADCs for patients with treatment-refractory cancers. In this Review, we highlight advances in each ADC component (the monoclonal antibody, payload, linker and conjugation chemistry) and provide more-detailed discussions on selected examples of emerging novel ADCs of each format, enabled by engineering of one or more of these components.Antibody–drug conjugates (ADCs) are effective cancer drugs that have been approved for more than 20 specific indications. Nonetheless, acquired resistance and adverse events both limit the effectiveness of these agents. In this Review, the authors describe the development of novel ADC designs, including bispecific ADCs, probody–drug conjugates, immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs. all of which have the potential to address these challenges and provide more effective ADCs.
Journal Article
Economics : the user's guide
\"Unlike many economists, who present only one view of their discipline, Chang introduces a wide range of economic theories--from the Classical economists to the Behavioral economists, from the Marxists to the Austrians--revealing how each has its strengths and weaknesses and why there is no one correct way to explain economic behavior. Instead, by challenging received wisdom and exposing the myriad institutional, political, and technological forces that shape our economic world, Chang explains how our increasingly global and interconnected world works and is evolving. Economics: The User's Guide is a concise and expertly crafted guide to economic theories, and will give all who read it a clear and accurate picture of the global economy and how and why it affects our daily lives.\"--Jacket.
Book
An integrated expression atlas of miRNAs and their promoters in human and mouse
An atlas of microRNA expression patterns and regulators is produced by deep sequencing of short RNAs in human and mouse cells.
MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.
Journal Article
Lovecidal: Walking with the Disappeared
In this new work, renowned feminist filmmaker and postcolonial theorist Trinh T. Minh-ha offers a lyrical, philosophical meditation on the global state of endless war and the violence inflicted by the imperial need to claim victory. She discusses the rise of the police state as linked, for example, to U.S. military intervention in Iraq and Afghanistan, or to China's occupation of Tibet, examining legacies of earlier campaigns and the residual effects of the war on terror. She also takes up the shifting dynamics of peoples' resistance to acts of militarism and surveillance as well as social media and its capacity to inform and mobilize citizens around the world. At once an engaging treatise and a creative gesture, Lovecidal probes the physical and psychic conditions of the world and shows us a society that is profoundly heartsick. Taking up with those who march both as and for the oppressedwho walk with the disappeared to help carry them forwardTrinh T. Minh-ha engages the spiritual and affective dimensions of a civilization organized around the rubrics of nonstop governmental subjugation, economic austerity, and highly technologized military conflict. In doing so, she clears a path for us to walk upon. Along with our every step, the world of the disappeared lives on.
eBook
Nanjing requiem
During the 1937 attack on Nanjing, American missionary and women's college dean Minnie Vautrin decides to remain at her school during a violent Japanese attack that renders the school a refugee center for ten thousand women and children.
Book
The mCME Project: A Randomized Controlled Trial of an SMS-Based Continuing Medical Education Intervention for Improving Medical Knowledge among Vietnamese Community Based Physicians’ Assistants
Community health workers (CHWs) provide critical services to underserved populations in low and middle-income countries, but maintaining CHW's clinical knowledge through formal continuing medical education (CME) activities is challenging and rarely occurs. We tested whether a Short Message Service (SMS)-based mobile CME (mCME) intervention could improve medical knowledge among a cadre of Vietnamese CHWs (Community Based Physician's Assistants-CBPAs) who are the leading providers of primary medical care for rural underserved populations.
The mCME Project was a three arm randomized controlled trial. Group 1 served as controls while Groups 2 and 3 experienced two models of the mCME intervention. Group 2 (passive model) participants received a daily SMS bullet point, and were required to reply to the text to acknowledge receipt; Group 3 (interactive model) participants received an SMS in multiple choice question format addressing the same thematic area as Group 2, entering an answer (A, B, C or D) in their response. The server provided feedback immediately informing the participant whether the answer was correct. Effectiveness was based on standardized examination scores measured at baseline and endline (six months later). Secondary outcomes included job satisfaction and self-efficacy.
638 CBPAs were enrolled, randomized, and tested at baseline, with 592 returning at endline (93.7%). Baseline scores were similar across all three groups. Over the next six months, participation of Groups 2 and 3 remained high; they responded to >75% of messages. Group 3 participants answered 43% of the daily SMS questions correctly, but their performance did not improve over time. At endline, the CBPAs reported high satisfaction with the mCME intervention, and deemed the SMS messages highly relevant. However, endline exam scores did not increase over baseline, and did not differ between the three groups. Job satisfaction and self-efficacy scores also did not improve. Average times spent on self-study per week did not increase, and the kinds of knowledge resources used by the CBPAs did not differ between the three groups; textbooks, while widely available, were seldom used.
The SMS-based mCME intervention, while feasible and acceptable, did not result in increased medical knowledge. We hypothesize that this was because the intervention failed to stimulate lateral learning. For an intervention of this kind to be effective, it will be essential to find more effective ways to couple SMS as a stimulus to promote increased self-study behaviors.
ClinicalTrials.gov NCT02381743.
Journal Article
بادي كلارك هاهاها
بادی کلارک هاهاها في روايته الحائزة على جائزة البوكر الدولية عام ١٩٩٣، يحكى لنا المؤلف رودي دويل من خلال كلمات وأعين بطله ذى الأعوام التسعة (بادي كلارك)، عن ضواحى مدينة دبلن في الستينيات، وعن مغامرات الصبية في الشوارع الخلفية بين بيوت الضواحى الجديدة التى تبنيها الشركة. يحكى لنا عن ملل فصول المدرسة وحماس اللعب في الشوارع ودراما العلاقات الأسرية وصراعات السلطة بين الأصدقاء المستترة في شكل ألعاب طفولية. بادي) كلارك ها ها ها) رواية غير تقليدية، مرحة أحيانا وتراجيدية أحيانا وغير تقليدية طوال الوقت، تصور الطفولة بعين دقيقة وإحكام بالغ، حتى تكاد تحسب مؤلفها في التاسعة من عمره حقا، لكنها ذلك ليست رواية أطفال بالمرة، فالواقع الذى يفصح عن نفسه بين سطورها فيه كل قسوة الحياة التي يعانى منها الجميع، كبار وصغار.
Book
Comparative Analysis of Audio Processing Techniques on Doppler Radar Signature of Human Walking Motion Using CNN Models
Artificial intelligence (AI) radar technology offers several advantages over other technologies, including low cost, privacy assurance, high accuracy, and environmental resilience. One challenge faced by AI radar technology is the high cost of equipment and the lack of radar datasets for deep-learning model training. Moreover, conventional radar signal processing methods have the obstacles of poor resolution or complex computation. Therefore, this paper discusses an innovative approach in the integration of radar technology and machine learning for effective surveillance systems that can surpass the aforementioned limitations. This approach is detailed into three steps: signal acquisition, signal processing, and feature-based classification. A hardware prototype of the signal acquisition circuitry was designed for a Continuous Wave (CW) K-24 GHz frequency band radar sensor. The collected radar motion data was categorized into non-human motion, human walking, and human walking without arm swing. Three signal processing techniques, namely short-time Fourier transform (STFT), mel spectrogram, and mel frequency cepstral coefficients (MFCCs), were employed. The latter two are typically used for audio processing, but in this study, they were proposed to obtain micro-Doppler spectrograms for all motion data. The obtained micro-Doppler spectrograms were then fed to a simplified 2D convolutional neural networks (CNNs) architecture for feature extraction and classification. Additionally, artificial neural networks (ANNs) and 1D CNN models were implemented for comparative analysis on various aspects. The experimental results demonstrated that the 2D CNN model trained on the MFCC feature outperformed the other two methods. The accuracy rate of the object classification models trained on micro-Doppler features was 97.93%, indicating the effectiveness of the proposed approach.
Journal Article