Establishing Quantitative Metrics for Soil Health: An In-Situ Method for Quantifying Soil Structure

Quantitative soil structure metrics would be beneficial not only for assessing soil health, but also optimizing biophysical models. A rapid and reliable field method of soil structure measurement that can obtain quantitative metrics, is needed so that the effects of land management on soil structure can be measured in situ. Successful methods and analyses quantifying soil structure of intact soil profiles transported to the lab have been established. The research objective of this thesis is to develop a method for quick and accurate field quantification of soil structure using 3D scanning technology. Once the field methodologies were established, scans of soil surface horizons were collected from three areas across the Blackland Prairie Major Land Resource Area of Texas, USA. In each of these three areas, scans were collected in triplicate from fields under three land management categories: conventional till, no till, and perennial. Measurements of bulk density and other physical properties of the scanned soil were made also. Two scanner resolutions for field data collection were evaluated; Wide (0.4 mm) and Macro (0.1 mm). Wide scan collection and processing was quicker by approximately 70 minutes and produced similar results to Macro. Tessellation analysis of the soil face topography data from the scans yielded useful quantitative soil structure data that were assessed in linking changes in soil condition to changes in management practices. Average tessellation polygon areas showed statistical structural differences between soil horizons (p = 0.002) and a statistical difference between managements in one of the studied areas (p = 0.03). Other measured soil properties did not show strong correlations with tessellation results or significant differences by management. The tessellation analysis was proven to be a successful analytic data method but needs further refinement for more widespread use in agricultural applications

Different adaptations of IgG effector function in human and non-human primates and implications for therapeutic antibody treatment

Safety of human therapeutic antibodies is generally assessed in non-human primates. While IgG1 shows identical FcγR interaction and effector function profile in both species, fundamental differences in the IgG2 and IgG4 antibody subclasses were found between the two species. Granulocytes, the main effector cells against IgG2 and IgG4 opsonized bacteria and parasites, do not express FcγRIIIb, but show higher levels of FcγRII in cynomolgus monkey. In humans, IgG2 and IgG4 adapted a silent Fc region with weak binding to FcγR and effector functions, whereas in contrast cynomolgus monkey IgG2 and IgG4 display strong effector function as well as differences in IgG4 Fab arm exchange. To balance this shift toward activation, the cynomolgus inhibitory FcγRIIb shows strongly increased affinity for IgG2. In view of these findings, in vitro and in vivo results for human IgG2 and IgG4 obtained in the cynomolgus monkey have to be cautiously interpreted, whereas effector function related effects of human IgG1 antibodies are expected to be predictable for man

Reductions in visceral fat during weight loss and walking are associated with improvements inV˙ o

The accumulation of visceral fat is independently associated with an increased risk for cardiovascular disease. The aim of this study was to determine whether the loss of visceral adipose tissue area (VAT; computed tomography) is related to improvements in maximal O2 uptake (V˙o 2 max) during a weight loss (250–350 kcal/day deficit) and walking (3 days/wk, 30–40 min) intervention. Forty obese [body fat 47 ± 1 (SE) %], sedentary (V˙o 2 max 19 ± 1 ml · kg−1 · min−1) postmenopausal women (age 62 ± 1 yr) participated in the study. The intervention resulted in significant declines in body weight (−8%), total fat mass (dual-energy X-ray absorptiometry; −17%), VAT (−17%), and subcutaneous adipose tissue area (−17%) with no change in lean body mass (all P < 0.001). Women with an average 10% increase in V˙o 2 max reduced VAT by an average of 20%, whereas those who did not increaseV˙o 2 max decreased VAT by only 10%, despite comparable reductions in body fat, fat mass, and subcutaneous adipose tissue area. The decrease in VAT was independently related to the change in V˙o 2 max( r 2 = 0.22; P < 0.01) and fat mass ( r 2 = 0.08; P = 0.05). These data indicate that greater improvements inV˙o 2 max with weight loss and walking are associated with greater reductions in visceral adiposity in obese postmenopausal women

Development of anti-CD32b antibodies with enhanced Fc function for the treatment of B and plasma cell malignancies

The sole inhibitory Fcγ receptor CD32b (FcγR2b) is expressed throughout B and plasma cell development and on their malignant counterparts with the highest expression found on multiple myeloma. Additionally, CD32b expression on tumor cells is known to sequester IgG Fc whereby providing a mechanism of resistance to therapeutic monoclonal antibodies (mAb) with Fc dependent activity. Taken together, CD32b represents an attractive tumor antigen for targeting with a mAb. To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. The complementarity-determining regions (CDRs) of these antibodies bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcR on immune effector cells. NVS32b mAbs selectively depletes CD32b+ healthy and malignant B cells but spares myeloid cells and CD32a+ cells. These antibodies mediate potent killing of opsonized cells via antibody dependent cellular cytotoxicity and phagocytosis (ADCC & ADCP), as well as complement dependent cytotoxicity (CDC). Additionally, NVS32b CDRs block the CD32b Fc binding domain, thereby minimizing CD32b mediated resistance to therapeutic mAbs with Fc dependent activity, including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b positive xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor microenvironment and enhancement of DC maturation in response to immune-complexes. The activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed on samples from CLL and MM patients. NVS32b mAbs demonstrated great therapeutic potential, as a single agent or in combination with other mAb therapeutics

Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

The sole inhibitory Fcγ receptor CD32b (FcγR2b) is expressed throughout B and plasma cell development and on their malignant counterparts with the highest expression found on multiple myeloma. Additionally, CD32b expression on tumor cells is known to sequester IgG Fc whereby providing a mechanism of resistance to therapeutic monoclonal antibodies (mAb) with Fc dependent activity. Taken together, CD32b represents an attractive tumor antigen for targeting with a mAb. To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. The complementarity-determining regions (CDRs) of these antibodies bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcR on immune effector cells. NVS32b mAbs selectively depletes CD32b+ healthy and malignant B cells but spares myeloid cells and CD32a+ cells. These antibodies mediate potent killing of opsonized cells via antibody dependent cellular cytotoxicity and phagocytosis (ADCC & ADCP), as well as complement dependent cytotoxicity (CDC). Additionally, NVS32b CDRs block the CD32b Fc binding domain, thereby minimizing CD32b mediated resistance to therapeutic mAbs with Fc dependent activity, including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b positive xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor microenvironment and enhancement of DC maturation in response to immune-complexes. The activity of NVS32b mAbs on CD32b+ primary malignant B and plasma cells was confirmed on samples from CLL and MM patients. NVS32b mAbs demonstrated great therapeutic potential, as a single agent or in combination with other mAb therapeutics

Development of anti-CD32b antibodies with enhanced Fc function for the treatment of B and plasma cell malignancies

The sole inhibitory Fcg receptor CD32b (Fcg RIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of Fcg RIIIa on immune effector cells. The NVS32b mAbs selectively target CD32bþ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32bþ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc–binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32bþ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32bþ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32bþ malignant cells

Mechanical Control of Electroresistive Switching

Hysteretic metal–insulator transitions (MIT) mediated by ionic dynamics or ferroic phase transitions underpin emergent applications for nonvolatile memories and logic devices. The vast majority of applications and studies have explored the MIT coupled to the electric field or temperarture. Here, we argue that MIT coupled to ionic dynamics should be controlled by mechanical stimuli, the behavior we refer to as the piezochemical effect. We verify this effect experimentally and demonstrate that it allows both studying materials physics and enabling novel data storage technologies with mechanical writing and current-based readout