Monte Carlo simulation-guided design for size-tuned tumor spheroid formation in 3D printed microwells.

Tumor spheroid models have garnered significant attention in recent years as they can efficiently mimic in vivo models, and in addition, they offer a more controlled and reproducible environment for evaluating the efficacy of cancer drugs. In this study, we present the design and fabrication of a micromold template to form multicellular spheroids in a high-throughput and controlled-sized fashion. Briefly, polydimethylsiloxane-based micromolds at varying sizes and geometry were fabricated via soft lithography using 3D-printed molds as negative templates.

Data-driven H control of constrained systems: An application to bilateral teleoperation system.

A novel, identification-free, data-driven (DD) H control method is presented for discrete-time (DT) linear time-invariant (LTI) systems under physical limitations and norm-bounded disturbances. The presented approach does not demand information on system matrices or any measurements of disturbance affecting the system. The only information needed to develop a static state-feedback (SF) controller is the bounds on disturbances, states and control signals.

Molecular epidemiology of simian immunodeficiency virus SIVsm in U.S. primate centers unravels the origin of SIVmac and SIVstm.

Retrospective molecular epidemiology was performed on samples from four sooty mangabey (SM) colonies in the United States to characterize simian immunodeficiency virus SIVsm diversity in SMs and to trace virus circulation among different primate centers (PCs) over the past 30 years. The following SIVsm sequences were collected from different monkeys: 55 SIVsm isolates from the Tulane PC sampled between 1984 and 2004, 10 SIVsm isolates from the Yerkes PC sampled in 2002, 7 SIVsm isolates from the New Iberia PC sampled between 1979 and 1986, and 8 SIVsm isolates from the California PC sampled between 1975 and 1977. PCR and sequencing were done to characterize the gag, pol, and env gp36 genes.

Molecular epidemiology of simian T-cell lymphotropic virus type 1 in wild and captive sooty mangabeys.

A study was conducted to evaluate the prevalence and diversity of simian T-cell lymphotropic virus (STLV) isolates within the long-established Tulane National Primate Research Center (TNPRC) colony of sooty mangabeys (SMs; Cercocebus atys). Serological analysis determined that 22 of 39 animals (56%) were positive for STLV type 1 (STLV-1). A second group of thirteen SM bush meat samples from Sierra Leone in Africa was also included and tested only by PCR.

Direct inoculation of simian immunodeficiency virus from sooty mangabeys in black mangabeys (Lophocebus aterrimus): first evidence of AIDS in a heterologous African species and different pathologic outcomes of experimental infection.

A unique opportunity for the study of the role of serial passage and cross-species transmission was offered by a series of experiments carried out at the Tulane National Primate Research Center in 1990. To develop an animal model for leprosy, three black mangabeys (BkMs) (Lophocebus aterrimus) were inoculated with lepromatous tissue that had been serially passaged in four sooty mangabeys (SMs) (Cercocebus atys). All three BkMs became infected with simian immunodeficiency virus from SMs (SIVsm) by day 30 postinoculation (p.

Classic AIDS in a sooty mangabey after an 18-year natural infection.

Prevailing theory holds that simian immunodeficiency virus (SIV) infections are nonpathogenic in their natural simian hosts and that lifelong infections persist without disease. Numerous studies have reported that SIV-infected sooty mangabeys (SMs; Cercocebus atys) remain disease free for up to 24 years despite relatively high levels of viral replication. Here, we report that classic AIDS developed after an 18-year incubation in an SM (E041) with a natural SIVsm infection.

Evidence for a rhesus monkey model of asymptomatic tuberculosis.

Rhesus monkeys (RM) were inoculated intrabronchially with graded doses of Mycobacterium tuberculosis (MTB) strains Erdman and H37Rv in an effort to produce a model of asymptomatic tuberculosis infection. Erdman strain produced active disease within 7-11 weeks regardless of dose. Low doses of H37Rv resulted in asymptomatic infections; high doses produced active disease within 11 weeks.

A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM).

Under-explored experimental topics related to integral mycobacterial vaccines for leprosy.

Many leprosy vaccine studies have utilized live or killed whole mycobacteria, such as Bacille Calmette-Guérin, Indian Cancer Research Center (ICRC) bacilli and Mycobacterium w either alone or in combination with killed Mycobacterium leprae. For Bacille Calmette-Guérin, the vaccine dose is generally that which gives the largest delayed-type hypersensitivity response with minimal side effects. The doses of other integral mycobacterial vaccines appear to be arbitrarily chosen.

Spectrum of manifestations of Mycobacterium tuberculosis infection in primates infected with SIV.

To characterize the manifestations of coinfection with M. tuberculosis and SIV infection, we studied 12 SIV-infected rhesus monkeys, six of which were infected intrabronchially with a low dose of Mycobacterium tuberculosis H37Rv. In the six coinfected animals, M.

Noninvasive detection of new simian immunodeficiency virus lineages in captive sooty mangabeys: ability to amplify virion RNA from fecal samples correlates with viral load in plasma.

The sooty mangabey (SM) (Cercocebus atys) is the natural host of a simian immunodeficiency virus, termed SIVsm, which gave rise to human immunodeficiency virus type 2. Data on the geographic distribution, prevalence, and genetic diversity of SIVsm in the wild remains limited. To address this issue, noninvasive strategies based on screening SM fecal and urine specimens for SIVsm-specific antibodies and virion RNA (vRNA) were developed, and the results were correlated with viral loads in plasma.

Anti-leprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: lepromin skin test results.

Groups of rhesus monkeys (RM) were vaccinated and boosted with living Mycobacterium bovis Bacillus Calmette-Guerin (BCG) or BCG + low dose (LD) heat-killed Mycobacterium leprae (HKML) or high dose (HD) HKML or were unvaccinated. Animals vaccinated with BCG + LD and HD HKML were lepromin skin tested 2 weeks after boosting. All groups were lepromin tested 37 and 46 months after challenge with live M.

Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of sooty mangabey monkeys (SMM) were vaccinated and boosted with Mycobacterium bovis bacillus Calmette-Guerin (BCG), or BCG + low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M.

Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys.

Groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (SIV)B670 alone; 2) Mycobacterium leprae alone; 3) SIV plus M. leprae on the same day; and 4) M. leprae 2 weeks after SIV.

Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of rhesus monkeys were vaccinated and boosted with Mycobacterium bovis bacillus Calmette Guerin (BCG) or BCG plus low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M.

Experimental leprosy in rhesus monkeys: transmission, susceptibility, clinical and immunological findings.

A total of 46 Rhesus monkeys (RM) was inoculated with Mycobacterium leprae (ML) and followed clinically and immunologically for extended periods. Twenty-one (45.7%) of the RM developed leprosy spanning the known leprosy spectrum, with six of 21 (28.

Spontaneous leprosy in a wild-caught cynomolgus macaque.

Naturally occurring Mycobacterium leprae has been previously documented in only two species of nonhuman primates from West Africa--the chimpanzee and the sooty mangabey. We report here the first known case of spontaneous leprosy in an Asian macaque. A wild-caught cynomolgus macaque imported from The Philippines developed a reaction to a tuberculin skin test after 3 years at the California Regional Primate Research Center (CRPRC), University of California-Davis, Davis, California, U.

Impaired responses to Mycobacterium leprae antigens in rhesus monkeys experimentally inoculated with simian immunodeficiency virus and M. leprae.

Seven of eight rhesus monkeys (RM) coinfected with simian immunodeficiency virus (SIV) and Mycobacterium leprae harboured acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites at times of humane sacrifice (up to 270 days post-M. leprae inoculation) due to SIV-induced debilitation or, in one long term survivor's case, to date over 3 years post-M. leprae inoculation.

Protective immunization of monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: clinical results.

Rhesus and sooty mangabey monkeys (RM and SMM) were vaccinated and boosted with BCG or BCG + low dose (LD) or high dose (HD) heat-killed Mycobacterium leprae (HKML). One group was not vaccinated. Except for a group of controls, all monkeys were challenged with live M.

Detection of IgA anti-PGL-I specific antigen to Mycobacterium leprae in mangabey monkeys inoculated with M. leprae.

Using sera from 4 pairs of mangabey monkeys inoculated with titrated doses of Mycobacterium leprae we demonstrated that IgA antibodies against M. leprae specific PGL-I antigen were present in 75% of inoculated monkey's sera. High IgA antibody was detected in 50% (3/6) of infected animals and all three developed lepromatous leprosy (LL).

Experimental leprosy in monkeys. I. Sooty mangabey monkeys: transmission, susceptibility, clinical and pathological findings.

A total of 31 sooty mangabey monkeys (SMM) (Cercocebus torquatus atys) inoculated by various routes with differing numbers of SMM-origin Mycobacterium leprae (ML) and 4 SMM inoculated with human-origin ML were observed for 4-12 years. SMM-origin ML was more pathogenic in SMM than human-origin ML. The spectrum of disease ranged from indeterminate to borderline and lepromatous in different animals.

Experimental leprosy in monkeys. II. Longitudinal serological observations in sooty mangabey monkeys.

In this study, 11 SMM were grouped and inoculated with differing doses of SMM-origin Mycobacterium leprae (ML) between 4.5 x 10(8) and 1 x 10(9) by either combined IV/IC routes or by IV or IC route alone. The combined route was the most effective in eliciting progressive, disseminated LL leprosy.

Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan.

To determine the association between leprosy and human retroviral infections, 57 leprosy patients, 39 leprosy contacts, and 500 pregnant women were investigated serologically for antibodies to human immunodeficiency virus type 1 (HIV) and human T cell lymphotropic virus (HTLV) types I and II. Antibodies to Mycobacterium leprae phenolic glycolipid I (PGL-I), and lipoarabinomannan (LAM) were also analyzed. A low prevalence of HIV-1 infection was observed among leprosy patients (3.