gebhart/patrepeval huggingface dataset:
Protein Design by Directed Evolution (2008)

While nature evolved polypeptides over billions of years, protein design by evolutionary mimicry is progressing at a far more rapid pace. The mutation, selection, and amplification steps of the evolutionary cycle may be imitated in the laboratory using existing proteins, or molecules created de novo from random sequence space, as starting templates. However, the astronomically large number of possible polypeptide sequences remains an obstacle to identifying and isolating functionally interesting variants. Intelligently designed libraries and improved search techniques are consequently important for future advances. In this regard, combining experimental and computational methods holds particular promise for the creation of tailored protein receptors and catalysts for tasks unimagined by nature.
DNA Amplification for Direct Detection of HIV-1 in DNA of Peripheral Blood Mononuclear Cells (1988)

By means of a selective DNA amplification technique called polymerase chain reaction, proviral sequences of the human immunodeficiency virus (HIV-1) were identified directly in DNA isolated from peripheral blood mononuclear cells (PBMCs) of persons seropositive but not in DNA isolated from PBMCs of persons seronegative for the virus. Primer pairs from multiple regions of the HIV-1 genome were used to achieve maximum sensitivity of provirus detection. HIV-1 sequences were detected in 100% of DNA specimens from seropositive, homosexual men from whom the virus was isolated by coculture, but in none of the DNA specimens from a control group of seronegative, virus culture-negative persons. However, HIV-1 sequences were detected in 64% of DNA specimens from seropositive, virus culture-negative homosexual men. This method of DNA amplification made it possible to obtain results within 3 days, whereas virus isolation takes up to 3 to 4 weeks. The method may therefore be used to complement or replace virus isolation as a routine means of determining HIV-1 infection.
Stress Urinary Incontinence due to Prescription Medications: Alpha-Blockers and Angiotensin Converting Enzyme Inhibitors (1998)

Gynecologists should be aware of the unexpected side effects of medications on the lower urinary tract.
Rac1 Mediates Collapsin-1-Induced Growth Cone Collapse (1997)

Collapsin-1 or semaphorin III(D) inhibits axonal outgrowth by collapsing the lamellipodial and filopodial structures of the neuronal growth cones. Because growth cone collapse is associated with actin depolymerization, we considered whether small GTP-binding proteins of the rho subfamily might participate in collapsin-1 signal transduction. Recombinant rho, rac1, and cdc42 proteins were triturated into embryonic chick (DRG) neurons. Constitutively active rac1 increases the proportion of collapsed growth cones, and dominant negative rac1 inhibits collapsin-1-induced collapse of growth cones and collapsin-1 inhibition of neurite outgrowth. DRG neurons treated with dominant negative rac1 remain sensitive to myelin-induced growth cone collapse. Similar mutants of cdc42 do not alter growth cone structure, neurite elongation, or collapsin-1 sensitivity. Whereas the addition of activated rho has no effect, the inhibition of rho with Clostridium botulinum C3 transferase stimulates the outgrowth of DRG neurites. C3 transferase-treated growth cones exhibit little or no lamellipodial spreading and are minimally responsive to collapsin-1 and myelin. These data demonstrate a prominent role for rho and rac1 in modulating growth cone motility and indicate that rac1 may mediate collapsin-1 action.
Measurement of the Glial Fibrillary Acidic Protein and Its Breakdown Products GFAP-BDP Biomarker for the Detection of Traumatic Brain Injury Compared to Computed Tomography and Magnetic Resonance Imaging (2014)

Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).
Tunable N-Path Notch Filters for Blocker Suppression: Modeling and Verification (2013)

N-path switched-RC circuits can realize filters with very high linearity and compression point while they are tunable by a clock frequency. In this paper, both differential and single-ended N-path notch filters are modeled and analyzed. Closed-form equations provide design equations for the main filtering characteristics and nonidealities such as: harmonic mixing, switch resistance, mismatch and phase imbalance, clock rise and fall times, noise, and insertion loss. Both an eight-path single-ended and differential notch filter are implemented in 65-nm CMOS technology. The notch center frequency, which is determined by the switching frequency, is tunable from 0.1 to 1.2 GHz. In a 50-Ω environment, the N-path filters provide power matching in the passband with an insertion loss of 1.4-2.8 dB. The rejection at the notch frequency is 21-24 dB, P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1 dB</sub> > +2 dBm, and IIP3 > +17 dBm.
Duration of effects of dietary fish oil supplementation on serum eicosapentaenoic acid and docosahexaenoic acid concentrations in dogs. (1998)

Studies of the effects of fish oil supplementation that use a crossover design should allow for an appropriate washout period.
A subgroup-specific antigenic site in the G protein of respiratory syncytial virus forms a disulfide-bonded loop (1990)

An antigenic site (represented by 15 amino acids, residues 174 to 188, designated peptide 12) of the large glycoprotein G of respiratory syncytial virus was demonstrated to be subgroup specific in peptide enzyme-linked immunosorbent assay tests with murine monoclonal antibodies and human postinfection sera. The role of individual amino acids in this subgroup-specific site was determined by use of single-amino-acid-deletion sets of peptides. When monoclonal antibodies were reacted with the deletion sets, a broad amino acid dependence of 11 or 12 residues, Cys-176 (Ile-175 in subgroup B) to Cys-186, was found. Human postinfection sera exhibited a narrower reaction profile (for subgroup A, Cys-182 to Trp-183; for subgroup B, Cys-176 to Lys-183). Reduction of peptides on microtiter plates by treatment with dithiothreitol completely destroyed their antigenic activity in tests with monoclonal antibodies and human postinfection sera of subgroup B. A variant of peptide 12 containing all four cysteines of the G protein (represented by 16 amino acids, residues 172 to 187, designated peptide 12var) also was subgroup specific. We concluded that the activity of the antigenic site in tests with monoclonal antibodies for subgroups A and B appears to depend on intrapeptide disulfide bonds. Reactions with postinfection sera of subgroup B also may depend on a disulfide bond. In contrast, postinfection sera of subgroup A appeared to have the capacity to identify a subgroup-specific site in a linear form of the selected 15-amino-acid-long peptide. Treatment of peptides with dithiothreitol had no effect on their antigenic activity in tests with human postinfection sera of subgroup A. These findings have relevance for molecular engineering of peptide antigens for use in respiratory syncytial virus subgroup-specific site-directed serology.
CD16- CD56+ natural killer cells after bone marrow transplantation (1992)

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.
Specificity of phosphatidylserine-containing membrane binding sites for factor VIII. Studies with model membranes supported by glass microspheres (lipospheres). (1992)

Factor VIII functions in an enzyme complex upon the activated platelet membrane where phosphatidylserine exposure correlates with expression of receptors for factor VIII. To evaluate the specificity of phosphatidylserine-containing membrane binding sites for factor VIII, we have developed a novel membrane model in which phospholipid bilayers are supported by glass microspheres (lipospheres). The binding of fluorescein-labeled factor VIII to lipospheres with membranes of 15% phosphatidylserine was equivalent to binding to phospholipid vesicles (KD = 4.8 nM). Purified von Willebrand factor (vWf), a carrier protein for factor VIII, decreased membrane binding of factor VIII with a Ki of 10 micrograms/ml. Likewise, normal plasma decreased bound factor VIII by more than 90% whereas plasma lacking vWf decreased the binding of factor VIII by only 20%. Proteolytic activation of factor VIII by thrombin, which releases factor VIII from vWf, increased liposphere binding in the presence of vWf and in the presence of normal plasma. Although factor V is homologous to factor VIII and binds to lipospheres with the same affinity, purified factor V was not an efficient competitor for the membrane binding sites of factor VIII. These results indicate that phosphatidylserine-containing membrane sites have sufficient specificity to select thrombin-activated factor VIII from the range of phospholipid-binding proteins in plasma.
Inter-Technology Backscatter: Towards Internet Connectivity for Implanted Devices (2016)

We introduce inter-technology backscatter, a novel approach that transforms wireless transmissions from one technology to another, on the air. Specifically, we show for the first time that Bluetooth transmissions can be used to create Wi-Fi and ZigBee-compatible signals using backscatter communication. Since Bluetooth, Wi-Fi and ZigBee radios are widely available, this approach enables a backscatter design that works using only commodity devices. We build prototype backscatter hardware using an FPGA and experiment with various Wi-Fi, Bluetooth and ZigBee devices. Our experiments show we can create 2-11 Mbps Wi-Fi standards-compliant signals by backscattering Bluetooth transmissions. To show the generality of our approach, we also demonstrate generation of standards-complaint ZigBee signals by backscattering Bluetooth transmissions. Finally, we build proof-of-concepts for previously infeasible applications including the first contact lens form-factor antenna prototype and an implantable neural recording interface that communicate directly with commodity devices such as smartphones and watches, thus enabling the vision of Internet connected implanted devices.
Expression of the tpr Protease Gene of Porphyromonas gingivalis Is Regulated by Peptide Nutrients (1998)

The Tpr protease of Porphyromonas gingivalis W83 is a membrane-associated enzyme capable of hydrolyzing chromogenic substrates for trypsin and bacterial collagenases. A previous study by us indicated that Tpr expression was increased under conditions of nutrient limitation. In the present study, we further characterized expression of the tpr gene using a tpr::lacZ reporter gene construct under a range of nutrient conditions. In P. gingivalis, transcription of tpr was initiated 215 bp upstream of the coding region and regulation of tpr expression was at the level of transcription. Deletion mutations in the tpr upstream region identified the promoter region immediately upstream of the transcription start site, determined by primer extension analysis. Three identical 17-bp direct repeats identified within the 5' end of tpr mRNA were involved in tpr regulation. In an Escherichia coli background, tpr transcription was initiated after an AT-rich region upstream of tpr but not at the P. gingivalis start site. Tpr expression in P. gingivalis was suppressed by the addition of peptide and protein nutrients to a peptide-limited growth medium but was only slightly affected by addition of free amino acids. Low-molecular-weight fractions of brain heart infusion rich in phenylalanine, proline, and alanine had the greatest inhibitory effects on expression of the tpr::lacZ construct. Addition of the dipeptide phenylalanyl-phenylalanine to the growth medium resulted in a 10-fold decrease in tpr expression. This suggests that specific phenylalanine-containing peptides are a major factor controlling Tpr expression. Neither hemin starvation, heat shock, nor pH change had significant effects on Tpr expression.
Stimulation of Peri-Implant Vascularization with Bone Marrow-Derived Progenitor Cells: Monitoring by In Vivo EPR Oximetry (2007)

The poorly vascularized fibrous capsule that develops around implantable biomedical devices (for drug delivery, biosensors, etc.) severely limits their applications. We tested the hypotheses that co-implantation of bone marrow-derived progenitor cells could stimulate the vascularization of implants. To assess the presence of functional peri-implant microvasculature, we developed a novel model of implanted device containing an oxygen (O(2))-sensing spin probe (detectable using electron paramagnetic resonance) placed inside a nanoporous filter-limited capsule. These devices were implanted subcutaneously in C57/Bl6 mice alone, with the addition of a Matrigel plug in front of the filter, or with the addition of Matrigel containing equal proportions of c-kit(+) and stem cell antigen-1(+) bone marrow-derived cells. Implants partial pressure of O(2) (pO(2)) were recorded non-invasively and periodically for up to 10 weeks. Tissue surrounding the implants was collected for immunohistochemistry. Initially, there were no differences in pO(2) between the experimental groups. After 3 weeks, the devices supplied with progenitor cells showed more than twice the O(2) concentrations as controls. This difference remained significant for 4 more weeks and then started to decrease slightly, still being 6 mmHg higher than in the controls at 10 weeks post-implantation. Collagen deposition was detected around the control implants, along with F4/80-positive macrophages and giant cells. In the plugs collected from the cell treatment group, we found an active process of adipogenesis, accompanied by neovascularization, and a highly vascularized adipose layer surrounding the implants. In conclusion, we successfully developed a cell therapy-type strategy to maintain vascularization around implanted devices using co-administration of bone marrow-derived progenitor cells, and we demonstrated a novel O(2)-sensing method to functionally monitor neovascularization in vivo.
Populations of Rhizobium leguminosarum biovars phaseoli and viceae in fields after bean or pea in rotation with nonlegumes (1989)

Populations of Rhizobium leguminosarum bv. phaesoli and bv. viceae in southern Alberta soils were measured over a period of 4 years using a most probable number method. Five fields cropped to bean (Phaseolus vulgaris L.), five fields cropped to pea (Pisum sativum L.), and two fields cropped to wheat were used as test sites. Legume crops had received appropriate legume inoculants. Fields were sampled in the fall of the crop year and in the spring of the following 3 years during which fields were cropped to nonlegumes or left fallow. Numbers of R. leguminosarum bv. phaseoli were 100 to 1000 times higher in fields that had been planted to bean than in fields that had been planted to pea or wheat. Fields that had been planted to pea maintained populations of R. leguminosarum bv. viceae 10 to 100 times higher than fields that had been planted to bean or wheat. Wheat fields, which had never had legumes grown in them, contained between 1 and 100 rhizobia per gram of soil of both biovars of R. leguminosarum, indicating that both biovars are native to southern Alberta soils. The numbers of rhizobia did not decrease in proportion to the population of other bacteria in the soil over the duration of the experiment. Plasmid profiles of soil Rhizobium isolates obtained in the last year of the experiment showed that none of the isolates had plasmid profiles similar to those of strains added as inoculants in the 1st year of the experiment. These results show that fields cropped to legumes and receiving rhizobial inoculants in this study maintained high populations of rhizobia for several years after harvest of the legume crop.Key words: Rhizobium leguminosarum bv. phaseoli, Rhizobium leguminosarum bv. viceae, nodule, plasmid profiles, inoculum potential, rhizobium competition.
Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. (1994)

We describe an approach to analyzing protein sequence databases that, starting from a single uncharacterized sequence or group of related sequences, generates blocks of conserved segments. The procedure involves iterative database scans with an evolving position-dependent weight matrix constructed from a coevolving set of aligned conserved segments. For each iteration, the expected distribution of matrix scores under a random model is used to set a cutoff score for the inclusion of a segment in the next iteration. This cutoff may be calculated to allow the chance inclusion of either a fixed number or a fixed proportion of false positive segments. With sufficiently high cutoff scores, the procedure converged for all alignment blocks studied, with varying numbers of iterations required. Different methods for calculating weight matrices from alignment blocks were compared. The most effective of those tested was a logarithm-of-odds, Bayesian-based approach that used prior residue probabilities calculated from a mixture of Dirichlet distributions. The procedure described was used to detect novel conserved motifs of potential biological importance.
Excretion of Non-infectious Virus Particles Lacking Glycoprotein H by a Temperature-sensitive Mutant of Herpes Simplex Virus Type 1: Evidence that gH Is Essential for Virion Infectivity (1988)

A temperature-sensitive mutant of herpes simplex virus type 1, tsQ26, was shown to contain an amino acid substitution in glycoprotein H (gH). The mutant entered cells efficiently at the non-permissive temperature and replicated to give nearly normal yields of intracellular infectivity. The intracellular virions contained, predominantly, an immature form of gH and no gH was found on the surface of infected cells. Excreted virions were devoid of gH and were not infectious. Virions excreted at the permissive temperature were infectious and contained gH and no loss of gH resulted from incubation of these virions at the non-permissive temperature. The temperature-sensitive phenotype apparently results from the loss of gH from virions during their transport to the cell surface, and since loss of gH is accompanied by loss of infectivity we conclude that gH is an essential component of the infectious virion.
The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors (2015)

The role of immune checkpoints in modulating the magnitude as well as the functional profile of T cell responses is increasingly understood in molecular detail. Antibody-mediated blockade of co-inhibitory receptors has been shown to restore T cell function in both chronic viral infections and cancer. The latter has been successfully translated to new therapeutic options in the treatment of cancer. Indeed, monoclonal antibodies blocking either CTLA-4 or PD-1 have recently been approved for the treatment of metastatic melanoma in the United States, Europe and Japan. In this commentary, we summarize and put into perspective five letters recently published back to back in the November 27 (2014) issue of Nature reporting on different immunological and clinical aspects of blockade of the PD-1/PD-L1 pathway in tumor bearing hosts. Notably, treatment with anti-PD-L1 blocking antibody was shown result in profound clinical responses in patients with several solid tumor including bladder, lung and head and neck carcinomas among others. These five simultaneous publications highlight the tremendous therapeutic potential of targeting the PD-1/PD-L1 immune checkpoint and emphasize the need to identify appropriate biomarkers to guide their optimal clinical application.
Patient-specific cutting guides for total knee arthroplasty (2017)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: