Explore the vast range of titles available.

The list of ADCs in the clinic continues to grow, bolstered by the success of first two marketed ADCs: ADCETRIS® and Kadcyla®. Currently, there are 40 ADCs in various phases of clinical development. However, only 34 of these have published their structures. Of the 34 disclosed structures, 24 of them use a linkage to the thiol of cysteines on the monoclonal antibody. The remaining 10 candidates utilize chemistry to surface lysines of the antibody. Due to the inherent heterogeneity of conjugation to the multiple lysines or cysteines found in mAbs, significant research efforts are now being directed toward the production of discrete, homogeneous ADC products, via site-specific conjugation. These site-specific conjugations may involve genetic engineering of the mAb to introduce discrete, available cysteines or non-natural amino acids with an orthogonally-reactive functional group handle such as an aldehyde, ketone, azido, or alkynyl tag. These site-specific approaches not only increase the homogeneity of ADCs but also enable novel bio-orthogonal chemistries that utilize reactive moieties other than thiol or amine. This broadens the diversity of linkers that can be utilized which will lead to better linker design in future generations of ADCs.

This paper presents a 14-bit hybrid column-parallel compact analog-to-digital converter (ADC) for the application of digital infrared focal plane arrays (IRFPAs) with compromised power and speed performance. The proposed hybrid ADC works in two phases: in the first phase, a 7-bit successive approximation register (SAR) ADC performs coarse quantization; in the second phase, a 7-bit single-slope (SS) ADC performs fine quantization to complete the residue voltage conversion. In this work, the number of unit capacitors is reduced to 1/128th of that of a conventional 14-bit SAR ADC, which is beneficial for the application of small pixel-pitch IRFPAs. In this work, a tradeoff segmented thermometer-coded digital-to-analog converter (DAC) is adopted in the first 7-bit coarse quantization process: the lower 3-bit is binary coded, and the upper 4-bit is thermometer coded. A thermometer-coded DAC can improve the linearity of ADC. Capacitor array matching can be incredibly relaxed compared with a binary-weight 14-bit SAR ADC, resulting in a noncalibration feature. Moreover, by sharing DAC and comparator analog circuits between the SAR ADC and the SS ADC, the power consumption and layout area are consequently reduced. The proposed hybrid ADC was fabricated using a 180 nm CMOS process. The measurement results show that the proposed ADC has a differential nonlinearity of −0.61/+0.84 LSB and a sampling rate of 120 kS/s. The developed ADC achieves a temporal noise of 1.7 LSBrms at a temperature of 77 K. In addition, the SNDR is 72.9 dB, and the ENOB is 11.82 bit, respectively. Total power consumption is 71 μW from supply voltages of 3.3 V (analog) and 1.8 V (digital).

The development of anti-HER2 agents has been one of the most meaningful advancements in the management of metastatic breast cancer, significantly improving survival outcomes. Despite the efficacy of anti-HER2 monoclonal antibodies, concurrent chemotherapy is still needed to maximize response. Antibody-drug conjugates (ADCs) are a class of therapeutics that combines an antigen-specific antibody backbone with a potent cytotoxic payload, resulting in an improved therapeutic index. Two anti-HER2 ADCs have been approved by the FDA with different indications in HER2-positive breast cancer. Ado-trastuzumab emtansine (T-DM1) was the first-in-class HER2-targeting ADC, initially approved in 2013 for metastatic patients who previously received trastuzumab and a taxane, and the label was expanded in 2019 to include adjuvant treatment of high-risk patients with residual disease after neoadjuvant taxane and trastuzumab-based therapy. In 2020, trastuzumab deruxtecan (T-DXd) was the second approved ADC for patients who had received at least 2 lines of anti-HER2-based therapy in the metastatic setting. The success of these two agents has transformed the treatment of HER2-positive breast cancer and has re-energized the field of ADC development. Given their advanced pharmaceutical properties, next-generation HER2-targeted ADCs have the potential to be active beyond traditional HER2-positive breast cancer and may be effective in cells with low expression of HER2 or ERBB2 mutations, opening a spectrum of new possible clinical applications. Ongoing challenges include improving target-specificity, optimizing the toxicity profile, and identifying biomarkers for patient selection. The aim of this review is to summarize the principal molecular, clinical, and safety characteristics of approved and experimental anti-HER2 ADCs, contextualizing the current and future landscape of drug development.

Diffusion-weighted imaging (DWI) is a technique used to probe the random microscopic motion of water protons in living tissue, represented by a parameter measurement of apparent diffusion coefficient (ADC) values. This study aimed to measure the ADC values of various fetal organs and placenta using 3T at various gestational ages. This was a prospective observational study. A total of 103 singleton pregnancies from 20 to 38 weeks of gestational age were included. Diffusion-weighted imaging was performed in the axial plane from the fetal head to the trunk with the following parameters: TR: 2000–2500 ms; TE: 88 ms; FOV: 250 mm; 256 matrix; slice thickness: 4 mm with a 0 mm gap; acquisition time: 1 min, 18 s. Diffusion gradient values were b = 0 and b = 700 s/mm 2 . ADC was measured in fetal brain regions (frontal white matter, occipital white matter, centrum semiovale, pons, thalamus, cerebellum, and fetal organs (lungs, kidney, and placenta). ANOVA was used to calculate the mean ADC values. Karl Pearson’s coefficient of correlation was used to evaluate the correlation between ADC values and increasing gestational age. The mean ADC values of brain regions were: frontal white matter (1.64 ± 0.08 × 10 − 3 mm 2 /s, F-39.10,p-<0.001), occipital white matter (1.64 ± 0.06 × 10 − 3 mm 2 /s, F-26.14, p-<0.001), centrum semiovale (1.62 ± 0.03 × 10 − 3  mm 2 /s, F-49.88,p-<0.001, pons (1.23 ± 0.09 × 10 − 3 mm 2 /s F-9.14,p-<0.001) ), Thalamus (1.21 ± 0.07 × 10 − 3 mm 2 /s, F-13.54,p-<0.001) and cerebellum (1.36 ± 0.10 × 10 − 3 mm 2 /s, F-4.19,p-<0.001). The mean ADC values of fetal organs were lung (1.92 ± 0.15 × 10 − 3 mm 2 /s, F-28.24, p-<0.001), kidney (1.34 ± 0.11 × 10 − 3 mm 2 /s, F-1.05, p- 0.37) and placenta (1.94 ± 0.11 × 10 − 3 mm 2 /s, F-160.33, p-<0.001). White-matter regions showed a significant positive correlation with increasing gestational age. Statistically, a negative correlation was observed between increasing gestational age and ADC measurements obtained in the thalamus, cerebellum, pons, and kidney. This will be one of the first few studies to provide the ADC values of the fetal brain and fetal organs using 3T MRI. The current study shows that diffusion-weighted MRI can offer a promising technique to evaluate the structural development of fetal organs and can potentially lead to a biomarker for predicting the functionality of the fetal organs in abnormalities.

An armed antibody (antibody–drug conjugate or ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg®) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved and late-stage ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, and their design for applications beyond oncology, to make ADCs the magic bullet that Paul Ehrlich dreamed of.

This paper presents a dual-residue pipelined successive approximation register (SAR) A/D converter (ADC) that relaxes the accuracy requirement for residue amplifications and thus enables use of only zero-crossing (ZX) signals for the benefits of power efficiency and technology scalability. The dual-residue architecture is illustrated with design of an 11b two-step pipelined ADC consisting of 8b coarse and 5b fine (with 2b over-range) SAR sub-ADCs, which resolve 2b and 1b per SAR conversion cycle, respectively. Two ZX signals (or dual-residues) in opposite polarities automatically available in each 2b SAR cycle are sampled and held at the end of the coarse conversion for use as the full-scale reference for the fine SAR that quantizes a fixed input of zero. Simulations show that the ADC in 45 nm CMOS using typical open-loop circuits for inter-stage residue operation can achieve ENOB > 10 at 400 MS/s and Schreier FoM = 171.4 dB without residue gain calibration.

Ultra-wideband (UWB) wireless communication is prospering as a powerful partner of the Internet-of-things (IoT). Due to the ongoing development of UWB wireless communications, the demand for high-speed and medium resolution analog-to-digital converters (ADCs) continues to grow. The successive approximation register (SAR) ADCs are the most powerful candidate to meet these demands, attracting both industries and academia. In particular, recent time-interleaved SAR ADCs show that multi-giga sample per second (GS/s) can be achieved by overcoming the challenges of high-speed implementation of existing SAR ADCs. However, there are still critical issues that need to be addressed before the time-interleaved SAR ADCs can be applied in real commercial applications. The most well-known problem is that the time-interleaved SAR ADC architecture requires multiple sub-ADCs, and the mismatches between these sub-ADCs can significantly degrade overall ADC performance. And one of the most difficult mismatches to solve is the sampling timing skew. Recently, research to solve this timing-skew problem has been intensively studied. In this paper, we focus on the cutting-edge timing-skew calibration technique using a window detector. Based on the pros and cons analysis of the existing techniques, we come up with an idea that increases the benefits of the window detector-based timing-skew calibration techniques and minimizes the power and area overheads. Finally, through the continuous development of this idea, we propose a timing-skew calibration technique using a comparator offset-based window detector. To demonstrate the effectiveness of the proposed technique, intensive works were performed, including the design of a 7-bit, 2.5 GS/s 5-channel time-interleaved SAR ADC and various simulations, and the results prove excellent efficacy of signal-to-noise and distortion ratio (SNDR) and spurious-free dynamic range (SFDR) of 40.79 dB and 48.97 dB at Nyquist frequency, respectively, while the proposed window detector occupies only 6.5% of the total active area, and consumes 11% of the total power.

This paper presents an adderless feed-forward incremental Δ Σ (I Δ Σ ) with asynchronous SAR (ASAR) that removes the need for in-column calibration by using global references, eliminates an additional summing amplifier and reduces the conversion time by using a multi-bit ASAR quantizer. The proposed I Δ Σ ADC is designed in 40 nm CMOS technology and is laid out compactly in a 5 μ m × 466 μ m column. According to post-layout simulations, the ADC achieves an input-referred noise of 85 μ V rms , a conversion time of 3.2 μ s (with DCDS) and a power consumption of 230 μ W. This results in a Walden FoM W of 234 fJ/conv.step and a FoM A = FoM W × A ADC of 0.54 fJ · mm 2 /conv.step, which demonstrates the feasibility of using the proposed architecture in CMOS image sensors.

This article reports on a compact and low-power CMOS readout circuit for bioelectrical signals based on a second-order delta-sigma modulator. The converter uses a voltage-controlled, oscillator-based quantizer, achieving second-order noise shaping with a single opamp-less integrator and minimal analog circuitry. A prototype has been implemented using 0.18 μm CMOS technology and includes two different variants of the same modulator topology. The main modulator has been optimized for low-noise, neural-action-potential detection in the 300 Hz–6 kHz band, with an input-referred noise of 5.0 μVrms, and occupies an area of 0.0045 mm2. An alternative configuration features a larger input stage to reduce low-frequency noise, achieving 8.7 μVrms in the 1 Hz–10 kHz band, and occupies an area of 0.006 mm2. The modulator is powered at 1.8 V with an estimated power consumption of 3.5 μW.

Anti-cancer antibody-drug conjugates (ADCs) aim to expand the therapeutic index of traditional chemotherapy by employing the targeting specificity of monoclonal antibodies (mAbs) to increase the efficiency of the delivery of potent cytotoxic agents to malignant cells. In the past three years, the number of ADCs approved by the Food and Drug Administration (FDA) has tripled. Although several ADCs have demonstrated sufficient efficacy and safety to warrant FDA approval, the clinical use of all ADCs leads to substantial toxicity in treated patients, and many ADCs have failed during clinical development due to their unacceptable toxicity profiles. Analysis of the clinical data has demonstrated that dose-limiting toxicities (DLTs) are often shared by different ADCs that deliver the same cytotoxic payload, independent of the antigen that is targeted and/or the type of cancer that is treated. DLTs are commonly associated with cells and tissues that do not express the targeted antigen (i.e., off-target toxicity), and often limit ADC dosage to levels below those required for optimal anti-cancer effects. In this manuscript, we review the fundamental mechanisms contributing to ADC toxicity, we summarize common ADC treatment-related adverse events, and we discuss several approaches to mitigating ADC toxicity.