Dark soliton detection using persistent homology.

Classifying images often requires manual identification of qualitative features. Machine learning approaches including convolutional neural networks can achieve accuracy comparable to human classifiers but require extensive data and computational resources to train. We show how a topological data analysis technique, persistent homology, can be used to rapidly and reliably identify qualitative features in experimental image data.

Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study.

Background: Ivermectin is a drug that has been shown to be active against coronavirus disease 19 (COVID-19) in previous studies. Healthcare personnel are highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to offer them ivermectin as a pre-exposure prophylaxis (PrEP) method.

Combination anti-coronavirus therapies based on nonlinear mathematical models.

Using nonlinear mathematical models and experimental data from laboratory and clinical studies, we have designed new combination therapies against COVID-19.

Acoustic vortex beams in synthetic magnetic fields.

We analyze the propagation of acoustic vortex beams in longitudinal synthetic magnetic fields. We show how to generate two field configurations using a fluid contained in circulating cylinders: a uniform synthetic magnetic field hosting Laguerre-Gauss modes, and an Aharonov-Bohm flux tube hosting Bessel beams. For non-paraxial beams we find qualitative differences from the well-studied case of electron vortex beams in magnetic fields, arising due to the vectorial nature of the acoustic wave's velocity field.

A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism.

Interleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (T). However, this therapy has been limited by off-target complications due to pathogenic cell expansion. Recent efforts have been focused on developing a more selective IL-2.

Factor XIa-specific IgG and a reversal agent to probe factor XI function in thrombosis and hemostasis.

Thrombosis is a major cause of morbidity and mortality. Current antithrombotic drugs are not ideal in that they must balance prevention of thrombosis against bleeding risk. Inhibition of coagulation factor XI (FXI) may offer an improvement over existing antithrombotic strategies by preventing some forms of thrombosis with lower bleeding risk.

Discovery of diverse and functional antibodies from large human repertoire antibody libraries.

Phage display antibody libraries have a proven track record for the discovery of therapeutic human antibodies, increasing the demand for large and diverse phage antibody libraries for the discovery of new therapeutics. We have constructed naïve antibody phage display libraries in both Fab and scFv formats, with each library having more than 250 billion clones that encompass the human antibody repertoire. These libraries show high fidelity in open reading frame and expression percentages, and their V-gene family distribution, VH-CDR3 length and amino acid usage mirror the natural diversity of human antibodies.

A new helper phage for improved monovalent display of Fab molecules.

Phage display technology is a powerful tool for the identification of novel antibodies for drug discovery. Phage display libraries have been constructed with massive diversity, but their use may be hindered by limited antibody display levels when rescued with the M13KO7 helper phage. Variants of M13KO7 have been constructed previously that increase the levels of display of rescued phage, but all produce phage that display multiple copies of the antibody fragment on their surface and have reduced titer and infectivity.

Improved visual acuity after frontalis sling surgery for simple congenital ptosis.

Introduction: Congenital ptosis is malpositioning of the eyelids that, when moderate or severe, can negatively affect visual development during its critical period, resulting in amblyopia: diminished visual acuity with no apparent organic cause. Early diagnosis and timely treatment are essential for preventing amblyopia. Congenital ptosis is uncommon but poses a challenge to any ophthalmologist; the only treatment is surgical.

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.

LFA-1 (alpha(L)beta(2)) mediates cell-cell and cell-extracellular matrix adhesions essential for immune and inflammatory responses. One critical mechanism regulating LFA-1 activity is the conformational change of the ligand-binding alpha(L) I domain from low-affinity (LA), closed form, to the high-affinity (HA), open form. Most known integrin antagonists bind both forms.

Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity.

Combinatorial libraries of rearranged hypervariable V(H) and V(L) sequences from nonimmunized human donors contain antigen specificities, including anti-self reactivities, created by random pairing of V(H)s and V(L)s. Somatic hypermutation of immunoglobulin genes, however, is critical in the generation of high-affinity antibodies in vivo and occurs only after immunization. Thus, in combinatorial phage display libraries from nonimmunized donors, high-affinity antibodies are rarely found.

Protein kinase C alpha protein expression is necessary for sustained erythropoietin production in human hepatocellular carcinoma (Hep3B) cells exposed to hypoxia.

Although protein kinase C (PKC) has been implicated as an effector of erythropoietin (EPO) production, its exact role is still uncertain. Hep3B human hepatocellular carcinoma cells were used for this study and were depleted of PKC in three different ways: long-term treatment with phorbol 12-myristate 13-acetate (PMA), selective inhibition with calphostin C, and treatment with PKCalpha antisense oligonucleotides. When EPO-producing Hep3B cells were incubated in 1% O2 (hypoxia) for 24 h, PMA treatment resulted in significant decreases in medium levels of EPO in Hep3B cell cultures at concentrations higher than 10 nM.

Post-transcriptional regulation of erythropoietin mRNA stability by erythropoietin mRNA-binding protein.

We have previously identified a sequence in the 3'-untranslated region (3'-UTR) of erythropoietin (Epo) mRNA which binds a protein(s), erythropoietin mRNA-binding protein (ERBP). A mutant lacking the ERBP binding site (EpoM) was generated. Hep3B cells were stably transfected with a wild-type Epo (EpoWT) cDNA or EpoM cDNA construct located downstream of a promoter of cytomegalovirus.

Interaction of erythropoietin RNA binding protein with erythropoietin RNA requires an association with heat shock protein 70.

Synthesis of erythropoietin (Epo), the glycoprotein hormone that regulates red blood cell formation, is induced in response to low oxygen stress (hypoxia), and is regulated at both transcriptional and post-transcriptional levels. We have previously described an Epo RNA binding protein (ERBP) which specifically binds to the 3'-untranslated region of Epo mRNA and is likely involved in the regulation of Epo mRNA stability. Since heat shock proteins (hsps) are induced in response to a variety of stresses, including hypoxia, we tested the possibility that hsps are involved in ERBP-Epo RNA complex formation.

Intracellular antibodies (intrabodies) for gene therapy of infectious diseases.

Intracellular antibodies (intrabodies) represent a new class of neutralizing molecules with a potential use in gene therapy. Intrabodies are engineered single-chain antibodies in which the variable domain of the heavy chain is joined to the variable domain of the light chain through a peptide linker, preserving the affinity of the parent antibody. Intrabodies are expressed inside cells and directed to different subcellular compartments where they can exert their function more effectively.

Changes in redox affect the activity of erythropoietin RNA binding protein.

We have previously identified a cytosolic protein, erythropoietin RNA binding protein (ERBP), which is up-regulated in certain tissues in response to hypoxia. To further characterize the interaction of ERBP and erythropoietin (EPO) mRNA, we have examined the role of reduction-oxidation in the EPO mRNA binding mechanism of ERBP isolated from human hepatoma cells (Hep3B). Reducing agents dithiothreitol (DTT) and 2-mercaptoethanol (2-ME) increased ERBP binding activity in a concentration-dependent manner, whereas the oxidizing agent, diamide, abolished ERBP binding activity.

Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein.

The mechanisms which control the production of erythropoietin (Epo) remain enigmatic. Recent data suggest that the half-time of Epo messenger RNA (mRNA) is increased by hypoxia in Hep 3B cells, a human hepatoma line. The post-transcriptional regulation of other rapidly degraded mRNAs is mediated by sequence-specific mRNA binding proteins.

Increased secretion of erythropoietin in human renal carcinoma cells in response to atrial natriuretic factor.

The present studies were undertaken to assess the effects of atrial natriuretic factor (ANF) on erythropoietin (Ep) secretion in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Human ANF produced a significant dose-related increase in Ep secretion at concentrations of 10(-7) and 10(-6) M when compared with vehicle controls. ANF (greater than or equal to 10(-9) M) also significantly increased the intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration after 5-min incubation with the RC cells.

Effect of ATP and amiloride on ANF binding and stimulation of cyclic GMP accumulation in rat glomerular membranes.

We investigated ANF binding and stimulation of cGMP accumulation in isolated rat glomerular membranes in the presence and absence of amiloride and ATP. Amiloride enhanced high affinity binding of ANF without affecting its stimulation of cGMP. In contrast ATP decreased binding and decreased basal cGMP accumulation without affecting the ability of ANF to stimulate cGMP.

Association of the atrial natriuretic factor receptor with guanylate cyclase in solubilized rat glomerular membranes.

The elution profile of solubilized rat glomerular membranes from a gel filtration column showed two peaks of 125I-ANF (atrial natriuretic factor) binding (367 +/- 21, 156 +/- 12 KDa). Over 85% of the total binding for the extract was in the 367 KDa peak. Guanylate cyclase activity was correlated with 125I-ANF specific binding.