gebhart/patrepeval huggingface dataset:
New Approaches for Isolation of Previously Uncultivated Oral Bacteria (2011)

A significant number of microorganisms from the human oral cavity remain uncultivated. This is a major impediment to the study of human health since some of the uncultivated species may be involved in a variety of systemic diseases. We used a range of innovations previously developed to cultivate microorganisms from the human oral cavity, focusing on anaerobic species. These innovations include (i) in vivo cultivation to specifically enrich for species actively growing in the oral cavity (the "minitrap" method), (ii) single-cell long-term cultivation to minimize the effect of fast-growing microorganisms, and (iii) modifications of conventional enrichment techniques, using media that did not contain sugar, including glucose. To enable cultivation of obligate anaerobes, we maintained strict anaerobic conditions in most of our cultivation experiments. We report that, on a per cell basis, the most successful recovery was achieved using minitrap enrichment (11%), followed by single-cell cultivation (3%) and conventional plating (1%). Taxonomically, the richest collection was obtained using the single-cell cultivation method, followed by minitrap and conventional enrichment, comprising representatives of 13, 9, and 4 genera, respectively. Interestingly, no single species was isolated by all three methods, indicating method complementarity. An important result is the isolation and maintenance in pure culture of 10 strains previously only known by their molecular signatures, as well as representatives of what are likely to be three new microbial genera. We conclude that the ensemble of new methods we introduced will likely help close the gap between cultivated and uncultivated species from the human oral cavity.
Improving CMOS-compatible Germanium photodetectors (2012)

We report design improvements for evanescently coupled Germanium photodetectors grown at low temperature. The resulting photodetectors with 10 μm Ge length manufactured in a commercial CMOS process achieve >0.8 A/W responsivity over the entire C-band, with a device capacitance of <7 fF based on measured data.
On a Sequence Arising in Algebraic Geometry (2005)

email We derive recurrence relations for the sequence of Maclaurin coefficients of the function χ = χ(t) satisfying (1 + χ) ln(1 + χ) = 2χ − t. 1
Metal mesoscopic contact as a source of plasmons for plasmonic nanocircuitries (2016)

We show that nanoscale metal contacts (constrictions) can serve as an efficient sources of plasmons for future nanoplasmonic integrated circuits. Electron, passing ballistically through nanoscale contact, can emit plasmons with the probability ~0.1 due to multiple collisions with walls of the constriction.
Selfish and Altruistic Bacterial Populations Maximize Fitness Under Stress by Local Segregation (2008)

Abstract Landscapes in ecology have a profound influence on the adaption and evolution of competing populations for resources. We are interested in how altruistic populations survive in the presence of selfish individuals in a non-stirred, closed and complex nutrient landscape. Well-stirred (landscape-free) but closed environments have a depressing future when selfish individuals arise in a population, a fate known as the tragedy of the Commons. Over-exploitation of a well-stirred communal habitat by selfish individuals which do not follow rules of communal self-regulation ends up in the elimination (extinction) of both the original altruistic inhabitants and the selfish population. In the context of bacterial population, the Commons tragedy that occurs is the consumption of limited resources by the individuals, resulting in metabolic stressing of the bacteria and growth advantages to be gained by defection from a ``social contract" of altruistic cooperation. There is no avoidance of this tragedy and the collapse of an original altruistic wild-type population by an emergent selfish population in a well-stirred but closed environment is inevitable. However, there is a fundamental difference between resource exploitation in a well-stirred homogenous commons and in a heterogenous landscape of nutrients which is not stirred. We show here using a non-stirred nanofabricated habitat landscape that altruists and selfish bacteria can in fact coexist, that they can maintain phenotype diversity and avoid the tragedy of the Commons. This emergent spatial segregation of competing populations under stress greatly changes, we believe, our perception of the true sophistication of bacterial response to stress and competition, and has broad implications for the adaptive strategies of higher organisms under stress in complex environments.
Reliability Challenges in Design and Operation of High Heat Powered Processors (2005)

Advances in processor design have been made possible in part by increases in the packaging density of electronics. At the same time, combination of increased power dissipation and packaging density has led to substantial growth in the chip and system heat fluxes and amplified complexity in electrical signal integrity and mechanical stack-up design in the recent years, particularly, in the high-end computers. With the trend towards miniaturization, heat removal, along with increased reliability requirements, has become a major bottleneck in product development, especially, in low profile systems, telecom servers and blades. Cooling of high heat flux components may require consideration of innovative open-loop, as well as plausible closed-loop, cooling designs for data centers. This paper addresses reliability aspects of thermal, electrical, mechanical, and interconnect design and long-life operation of high-end air-cooling, as well as feasible active open and closed-loop cooling technologies of high heat flux processors.
The Effects of Physiologic Dynamic Compression on Bone Healing Under External Fixation (1990)

The effects of early physiologic dynamic compression on fracture healing were studied in the dog. Transverse midtibial osteotomies were performed bilaterally and stabilized with a relatively rigid external fixation system in a neutralization mode (800 microns) to prevent compression of the osteotomy ends during weight bearing. On the 15th day, one osteotomy in each animal was subjected to dynamic compression through weight bearing by release of the fixator-telescoping mechanism (axial dynamization), while the other side remained unchanged as the control. Analysis of sequential roentgenograms showed that the callus distribution was more symmetric on the dynamic compression side. The two sides showed no significant differences in quantitative technetium-99 bone scans or in osteotomy-site blood flow. There were no statistical differences in new bone formation, bone porosity, or maximum torque between sides. The fixation had maintained the initially created osteotomy gap on the control side and tended to unite through a gap-healing mechanism. The dynamic compression side showed reduction in gap size and union by more of a contact-healing mechanism. There were no statistical differences in the rate of pin loosening, but its distribution according to pin location was significantly different between the two sides.
The New Scopes – Broadening the Colonoscopy Marketplace (2007)

Colonoscopy has been established as a screening tool for colorectal cancer and precursors in some countries. Efforts to improve instrument performance as well as patient comfort, safety and compliance have led to modifications of existing endoscopes as well as to the development of new scopes with different working mechanisms, including the colon capsule. While the former have not substantially changed performance, the true value of new scopes - partially single use and/or self propelling - can not be fully assessed, since they are either still under development and/or tested only in animals and in small groups of patients or volunteers. The colon capsule holds promise but has a too complicated preparatory regimen and too low a sensitivity at the moment. Future developments and further studies will show which of these techniques may complement or even replace traditional screening colonoscopy.
(CGRA4HPC) 2022 Invited Speaker: Pushing the Boundaries of HPC with the Integration of AI (2022)

As the market for high-performance computing continues to heat up there are constraints caused by the limited processing speed capacity of current architectures like CPUs and GPUs. Higher-resolution image processing requires massive computational capabilities making it challenging and costly for even the most innovative companies to succeed. SambaNova Systems has pioneered the ability to liberate organizations from the limitations of their legacy solutions — providing the core datacenter infrastructure to quickly build and deploy AI technologies at scale. Developers can run a 100-billion parameter model with ease, and enable highperformance processing of complex structures such as high-resolution images, pushing computer vision boundaries far beyond 4k. SambaNova Systems will showcase groundbreaking technology delivered by SambaNova's Reconfigurable Dataflow Architecture™ - an accelerated computing architecture designed to efficiently execute a broad range of AI and HPC applications.
Integrin‐dependent and ‐independent potentiation of L‐type Calcium Current (Cav1.2) by cell stretch (2011)

Stretch-induced contraction of VSM requires Ca influx through L-type Ca channels (Cav1.2). Integrins play a role in this process because alpha5 beta1 and alphaVbeta3 integrin blocking antibodies prevent myogenic constriction. Recent studies in our lab indicate that Cav1.2 current is potentiated by alpha5beta1 integrin activation and requires phosphorylation by PKA and c-Src of Cav1.2 C-terminal residues. To test whether Cav1.2 channels are mechanosensitive and the possible role of integrins in this process, patch clamp methods were used to investigate the properties of either native or heterologously expressed Cav1.2 cannels by stretch of single cells plated onto a flexible substrate. Thin silicone membranes were coated with either fibronectin (FN) or poly-l-lysine (PLL) to assess integrin-dependent and -independent responses, respectively, and stretched using two blunt micropipettes driven in equal and opposite directions by piezoelectric translators. Graded stretch to 130% of resting cell length induced graded increases in Cav1.2 current (up to 63%) in HEK 293 cells expressing the neuronal channel isoform (Cav1.2c). The increase in current was ~2-fold greater for cells adhering to FN than for cells on PLL. On FN, 130% longitudinal stretch of primary VSM cells induced ~50% increases in Cav1.2 current. However, the magnitude of stretch-activated Cav1.2 current was the same on FN or PLL for cells expressing a Cav1.2 construct containing two C-terminal mutations (Y2122F/S1901A) to prevent phosphorylation by PKA and c-Src, or for cells expressing a Cav1.2 construct with the C-terminus truncated. Our results suggest that the Cav1.2 channel can be potentiated by membrane stretch, with one component due to intrinsic mechanosensitivity of the channel and a second component due to signaling through an integrin-dependent process.
Peptide amidating activity in human bronchoalveolar lavage fluid (1996)

Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers in pulmonary epithelium is thought to be central to lung development, repair of injury and may contribute to carcinogenesis. In this study, we evaluate several candidate NE markers to determine the feasibility of prospective analysis of clinical specimens. The potential NE markers include the enzyme L-DOPA decarboxylase (DDC), the neuropeptide gastrin releasing peptide (GRP), and peptidyl-glycine alpha-amidating monooxygenase (PAM), the bifunctional enzyme responsible for the final bioactivation step of many neuropeptides. A comparison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidating activity may be an indicator of NE status. Bronchoalveolar lavage (BAL) fluid from subjects at risk of developing second primary lung cancer and from volunteers was obtained. The activity of the first PAM enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), ranged from not detectable to 507 pmol/h/mg protein in 57 specimens. The second PAM enzyme, peptidylamidoglycolate lyase (PAL), ranged from not detectable to 414 pmol/h/mg protein in 56 specimens. Using cluster analysis by the average linkage method, a group of enzyme values with PHM greater than 230 pmol/h/mg protein was determined. Long-term follow-up of these patients for new second primary lung cancers may help to determine the potential predictive value of PAM detected in the BAL fluid.
Local prolactin is a target to prevent expansion of basal/stem cells in prostate tumors (2010)

Androgen-independent recurrence is the major limit of androgen ablation therapy for prostate cancer. Identification of alternative pathways promoting prostate tumor growth is thus needed. Stat5 has been recently shown to promote human prostate cancer cell survival/proliferation and to be associated with early prostate cancer recurrence. Stat5 is the main signaling pathway triggered by prolactin (PRL), a growth factor whose local production is also increased in high-grade prostate cancers. The first aim of this study was to use prostate-specific PRL transgenic mice to address the mechanisms by which local PRL induces prostate tumorogenesis. We report that (i) Stat5 is the major signaling cascade triggered by local PRL in the mouse dorsal prostate, (ii) this model recapitulates prostate tumorogenesis from precancer lesions to invasive carcinoma, and (iii) tumorogenesis involves dramatic accumulation and abnormal spreading of p63-positive basal cells, and of stem cell antigen-1-positive cells identified as a stem/progenitor-like subpopulation. Because basal epithelial stem cells are proposed to serve as tumor-initiating cells, we challenged the relevance of local PRL as a previously unexplored therapeutic target. Using a double-transgenic approach, we show that Delta1-9-G129R-hPRL, a competitive PRL-receptor antagonist, prevented early stages of prostate tumorogenesis by reducing or inhibiting Stat5 activation, cell proliferation, abnormal basal-cell pattern, and frequency or grade of intraepithelial neoplasia. This study identifies PRL receptor/Stat5 as a unique pathway, initiating prostate tumorogenesis by altering basal-/stem-like cell subpopulations, and strongly supports the importance of further developing strategies to target locally overexpressed PRL in human prostate cancer.
Electrochemical Label-free Methods for Ultrasensitive MultiplexProtein Profiling of Infectious Diseases (2023)

Electrochemical detection methods are the more appropriate detection methods when it comes to the sensitive and specific determination of biomarkers. Biomarkers are the biological targets for disease diagnosis and monitoring. This review focuses on recent advances in label-free detection of biomarkers for infectious disease diagnosis. The current state of the art for rapid detection of infectious diseases and their clinical applications and challenges were discussed. Label-free electroanalytical methods are probably the most promising means to achieve this. We are currently in the early stages of the emerging technology of using label-free electrochemistry of proteins to develop biosensors. To date, antibody-based biosensors have been intensively developed, although many improvements in reproducibility and sensitivity are still needed. Moreover, there is no doubt that a growing number of aptamers and hopefully label-free biosensors based on nanomaterials will soon be used for disease diagnosis and therapy monitoring. And also here in this review article, we have discussed recent developments in the diagnosis of bacterial and viral infections, as well as the current status of the use of label-free electrochemical methods for monitoring inflammatory diseases.
Targeted intracellular delivery of Cas13 and Cas9 nucleases using bacterial toxin-based platforms (2022)

Targeted delivery of therapeutic proteins toward specific cells and across cell membranes remains major challenges. Here, we develop protein-based delivery systems utilizing detoxified single-chain bacterial toxins such as diphtheria toxin (DT) and botulinum neurotoxin (BoNT)-like toxin, BoNT/X, as carriers. The system can deliver large protein cargoes including Cas13a, CasRx, Cas9, and Cre recombinase into cells in a receptor-dependent manner, although delivery of ribonucleoproteins containing guide RNAs is not successful. Delivery of Cas13a and CasRx, together with guide RNA expression, reduces mRNAs encoding GFP, SARS-CoV-2 fragments, and endogenous proteins PPIB, KRAS, and CXCR4 in multiple cell lines. Delivery of Cre recombinase modifies the reporter loci in cells. Delivery of Cas9, together with guide RNA expression, generates mutations at the targeted genomic sites in cell lines and induced pluripotent stem cell (iPSC)-derived human neurons. These findings establish modular delivery systems based on single-chain bacterial toxins for delivery of membrane-impermeable therapeutics into targeted cells.
Improving Students' Understanding of Lock-In Amplifiers (2014)

A lock-in amplifier is a versatile instrument frequently used in physics research. However, many students struggle with the basic operating principles of a lock-in amplifier which can lead to a variety of difficulties. To improve students' understanding, we have been developing and evaluating a research-based tutorial which makes use of a computer simulation of a lock-in amplifier. The tutorial is based on a field-tested approach in which students realize their difficulties after predicting the outcome of simulated experiments involving a lock-in amplifier and check their predictions using the simulated lock-in amplifier. Then, the tutorial guides and helps students develop a coherent understanding of the basics of a lock-in amplifier. The tutorial development involved interviews with physics faculty members and graduate students and iteration of many versions of the tutorial with professors and graduate students. The student difficulties and the development and assessment of the research-based tutorial are discussed.
A Guide to Causal Parameters in Case-Control Designs: Targeted Maximum Likelihood Estimation (2008)

Researchers of uncommon diseases are often interested in assessing potential risk factors. Given the low incidence of disease, these studies are frequently case-control in design, as this allows for a sufficient number of cases to be obtained without extensive sampling and can increase efficiency. However, these case-control samples are then biased since the proportion of cases in the sample is not the same as the population of interest. Methods for analyzing case-control studies have focused on utilizing logistic regression models that provide conditional and not causal estimates of the odds ratio. This article will demonstrate the use of the prevalence probability and case-control weighted targeted maximum likelihood estimation (MLE), as described by van der Laan (2008), in order to obtain causal estimates of the parameters of interest (risk difference, relative risk, and odds ratio). It is meant to be used as a guide for researchers, with step-by-step directions to implement this methodology. We will also present simulation studies that show the improved efficiency of the case-control weighted targeted MLE compared to other techniques.
Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation (2014)

People over the age of 50 are at risk of osteoporotic fracture, which may lead to increased morbidity and mortality. Osteoclasts are responsible for bone resorption in bone-related disorders. Genipin is a well-known geniposide aglycon derived from Gardenia jasminoides, which has long been used in oriental medicine for controlling diverse conditions such as inflammation and infection. We aimed to evaluate the effects of genipin on RANKL-induced osteoclast differentiation and its mechanism of action. Genipin dose-dependently inhibited early stage RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) during culture. Genipin inhibited RANKL-induced IκB degradation and suppressed the mRNA expression of osteoclastic markers such as NFATc1, TRAP, and OSCAR in RANKL-treated BMMs, but did not affect c-Fos mRNA expression. Interestingly, genipin markedly inhibited c-Fos protein expression in BMMs, which was reversed in the presence of the proteosome inhibitor MG-132. Furthermore, genipin inhibited RANKL-mediated osteoclast differentiation, which was also rescued by overexpression of c-Fos and NFATc1 in BMMs. Taken together, our findings indicate that genipin down-regulated RANKL-induced osteoclast differentiation through inhibition of c-Fos protein proteolysis as well as inhibition of IκB degradation. Our findings indicate that genipin could be a useful drug candidate that lacks toxic side effects for the treatment of osteoporosis.
Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy (2018)

Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-α. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7-CpG did not. Clec9A-TNE loaded with pooled B16-F10 melanoma neoepitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neoepitopes. Clec9A-TNE encapsulating 6 neoepitopes significantly suppressed B16-F10 melanoma growth in a CD4+ T cell-dependent manner. Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help.
Protection levels of N95-level respirator substitutes proposed during the COVID-19 pandemic: safety concerns and quantitative evaluation procedures (2021)

Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes.