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One significant hurdle in additively manufacturing polymer-derived ceramics lies in reconciling the lower mechanical properties of additively manufactured parts compared to traditionally manufactured ceramics and PDCs. Here, a methodology is presented for evaluating the influence of layer thickness and exposure on polymer-derived ceramics within the constraints of commercially available software and hardware. Maximizing exposure within printable limitation of DLP processes, produced green bodies with the highest conversion, and resulted in improved pyrolysis outcomes, manufacturability, and most importantly ceramic strengths comparable to traditionally manufactured SiOC PDCs. Decreasing layer thickness and increasing total dwell time had a dramatic impact on mechanical properties, increasing flexural strength by more than 6x from 18 MPa at 100 μm layer thickness to 111 MPa at 10 μm layer thickness. Density of resultant ceramic also increased from 1.62 ± 0.03 g/cc to 2.3 ± 0.05 g/cc. This represented a large increase in mechanical strengths of PDCs produced via DLP in literature.

We present a unique case of neurosarcoidosis diagnosed based on thyroid biopsy and FDG PET (Fluorodeoxyglucose positron emission tomography) imaging. A patient presented for a second opinion after being placed in hospice for rapidly progressing dementia, presumed to be due to Creutzfeldt Jakob disease despite negative workup and was unable to perform activities of daily life or communicate with his wife. The patient underwent a workup including whole-body FDG PET, which showed hypermetabolic lymph nodes as well as a hypermetabolic nodule in the thyroid. Biopsy of the lymph nodes was nondiagnostic, but the thyroid biopsy tissue yielded a diagnosis of sarcoid. After ruling out other causes and reviewing the tissue pathology, the patient was diagnosed with systemic sarcoidosis with neurological involvement and started on infliximab with rapid improvement.

Abstract PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p

Abstract Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.

The 3D printing of pre-ceramic polymers that can be pyrolyzed into functional ceramics has recently become a focus for advanced ceramic applications requiring complex geometries. In this work, a new methodology for 3D printing SiCNO ceramic materials derived from a novel pre-ceramic photopolymer feedstock utilizing a thiol-ene reaction is introduced. The printed parts are pyrolyzed to amorphous SiCNO and the physical and mechanical properties of the final ceramic are measured. Pyrolysis of the pre-ceramic produced a SiCNO ceramic with 41% ceramic yield and shrinkage of 24% with a hardness measured at 6.6 GPa ± 0.3 GPa.

The use of engineering ceramics with intricate geometries is limited by manufacturing processes and lack ease of machinability of ceramics. Additive manufacturing of pre-ceramic polymers which are pyrolyzed into ceramics after 3D printing has recently been used to circumvent traditional manufacturing processes creating ceramics with complex geometries, however, mechanical characterization is limited. Polymer-derived ceramics and their green-body precursors are printed using digital light projection 3D printing in two orientations (0°- and 90°- to the build plate) and mechanically characterized. The results show that mechanical anisotropy exists both in the green-body polymer samples where the 0°-samples are stronger and stiffer than their 90°-counterparts and the final ceramics, where the stronger samples are fabricated at 90° despite isotropic hardness measurements. Through the manufacturing process, it was noted that samples undergoing pyrolysis built in the 90°-orientation have a pyrolysis survival rate of 94% whereas the 0°-samples showed a survival rate of 54%. The results suggest that the build-direction of 3D printed green-bodies plays a role in both material manufacturing and mechanical integrity of the final ceramic materials.

Abstract Studies evaluating Positron Emission Tomography scan after 2 cycles of chemotherapy (PET2) in newly diagnosed diffuse large B cell lymphoma (DLBCL) are heterogeneous in patient characteristics, treatments and have conflicting results. Here we report association of PET2 with outcomes in two large independent prospective cohorts of newly diagnosed DLBCL pts treated with two RCHOP-based regimens. The discovery cohort consisted of pts enrolled in single arm phase 2 MC078E study of lenalidomide with RCHOP (R2CHOP). The validation cohort consisted of RCHOP-treated pts from the Molecular Epidemiology Resource (MER) cohort. Pts who received 3-6 cycles of therapy and had PET2 were included in the study. Patients who progressed on PET2 were excluded. Revised response criteria 2007 were used to define PET2 response PET2 positive (PET2 + ) pts had inferior EFS [24-month EFS 45.5% vs 87.9%, HR 4.0, CI95 (2.1–7.9), p

Abstract Background F-18 fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) is used to assess response of non-Hodgkin lymphoma (NHL) to chimeric antigen receptor T cell (CAR-T) therapy. We sought to describe metabolic and volumetric PET prognostic factors at one month post-CAR-T and identify which patients with partial response (PR) or stable disease (SD) are most likely to subsequently achieve complete response (CR), and which will develop progressive disease (PD) and death. Methods Sixty-nine patients with NHL received axicabtagene ciloleucel CAR-T therapy. One-month post-CAR-T infusion and PET/CT scans were segmented with a fixed absolute SUV maximum (SUVMax) threshold of 2.5 using a semiautomated workflow with manual modification to exclude physiologic uptake as needed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVMax, and other lesion characteristics were calculated and associated with risk of PD and death. Results Patients with total MTV > 180 cc, presence of bone or parenchymal disease, SUVMax > 10, single lesion TLG > 245 g, or > 2 total lesions had increased risk of death. Patients with total MTV > 55 cc, total TLG > 250 cc, SUV Max > 10, or > 2 total lesions had increased risk of PD. For the subset of 28 patients with PR/SD, higher SUVMax was associated with increased risk of subsequent PD and death. While 86% of patients who had SUVMax ≥ 10 eventually had PD (HR 3.63, 1.13–11.66, p = 0.03), only 36% of those with SUVMax

Objective: To retrospectively evaluate the safety and efficacy of percutaneous image-guided mediastinal mass core-needle biopsy. Patients and Methods: Retrospective review of an institutionally maintained biopsy registry identified 337 computed tomography– or ultrasound-guided percutaneous mediastinal mass core needle biopsies between October 2002 and August 2017 in a single quaternary referral center. Mean patient age was 51 (range, 18 to 93) years. Procedural techniques, anticoagulation/antiplatelet therapy, and tumor anatomical characteristics were reviewed. Classification and gradation of complications was based on the Clavien-Dindo system. Diagnostic yield was defined as the ratio of diagnostic biopsy to all biopsies performed. Results: Mean tumor size was 59.2 (range, 10 to 180) mm with 89.9% (n=303) of lesions located in the prevascular (anterior) mediastinum. There was a single major complication (0.3%) of a symptomatic pneumothorax requiring intervention. There were seven (2.1%) minor complications, including three bleeding complications. A transpleural approach was the only variable associated with an increased complication rate (P

Abstract In human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation.

Background: Transversus abdominis plane block with liposomal bupivacaine has been studied as an effective method of reducing the need for postoperative opioids and increasing same-day discharge rates. However, less is known about the cost-effectiveness of this strategy relative to opioids alone for hernia repair. We performed an economic evaluation of these strategies using a computer simulation model. Methods: A decision tree was constructed to determine cost-effectiveness as measured by incremental cost-effectiveness ratios per quality-adjusted life-year. Base-case costs, quality-adjusted life-year values, and probabilities were derived from published studies and Medicare fee schedules. For input parameters for which we could not find values in the published literature, we used expert opinion. A 1-month time horizon was selected to focus on the immediate postoperative period. Finally, we performed 1-way, 2-way, and probabilistic sensitivity analyses. Results: The liposomal bupivacaine transversus abdominis plane block was a dominant strategy yielding a $456.75 decrease in cost and an 0.1 increase in quality-adjusted life-years relative to opioids alone. In 1-way sensitivity analysis of cost incremental cost-effectiveness ratio, values were most sensitive to variations in the amount saved by same-day discharge and the cost of bupivacaine. In probabilistic sensitivity analyses, transversus abdominis plane strategy was cost-effective at a willingness-to-pay threshold of $50,000/quality-adjusted life-year in 94.5% of iterations and at a willingness-to-pay threshold of $100,000/quality-adjusted life-year in 97.1% of iterations. Conclusion: The use of liposomal bupivacaine transversus abdominis plane block resulted in cost savings and improved quality-adjusted life-years in base-case analyses and was cost-effective at conventional willingness-to-pay thresholds in the majority of iterations in probabilistic sensitivity analyses.

Electric thruster materials are often subject to erosion during normal device operation. As a result of the ion sputtering process, surface properties can be affected or the underlying material may be exposed, possibly compromising performance and/or lifetime. It is therefore important to know both the energy and angle dependence of total sputter yield for relevant materials so that these effects can be predicted. In this study, we have obtained limited datasets on three materials with applications in electric propulsion development, thruster-spacecraft integration, and other technological areas—alumina, Hiperco 50, and HP boron nitride—in order to augment the material properties database. For each case, angular profiles were obtained at a single ion incidence energy, and energy dependence was explored at normal incidence. The datasets have been least squares fitted, and the results were interpreted.

Abstract Background To retrospectively analyze perilesional technetium Tc-99m MAA injection for intraoperative localization of atypical soft-tissue and bone lesions within a single tertiary referral center in order to determine technique, safety, and clinical utility of these procedures. Methods An IRB compliant, retrospective electronic chart review (2010–2017) exploring surgical excision of atypical (non-pulmonary, non-breast, non-sentinel node) lesions guided by Tc-99m MAA perilesional injection. Patient demographics, lesion location, lesion size, radiotracer injection technique, radiotracer injection complications, scintigraphy technique, scintigraphic quality, intraoperative time, lesion identification in surgery, and pathological diagnoses were recorded. Results Twenty-two atypical radiolocalization exams were identified. Lesion sites included rib (7), lymph node (4), abdominal wall (3), mesenteric (3), gallbladder fossa (1), retroperitoneum (1), parietal pleura (1), anterior mediastinum (1), and iliac bone (1). Average lesion size was 14 mm (range 5–23 mm). Eighteen (82%) radiotracer injections used computed tomography guidance and 4 (18%) used ultrasound guidance. The mean activity of Tc-99m MAA administered was 11.8 MBq (0.32 mCi). A 22-gauge needle was most often used for perilesional injection. No injection complications were reported. The lesions were identified with a hand-held gamma probe during surgery in 100% of cases. Of the samples sent to pathology, 100% were identified and given a diagnosis. Conclusion Radiolocalization of atypical lesions may be a valuable technique, guiding minimally invasive surgical removal of lesions that would otherwise be difficult to identify intraoperatively such as non-palpable rib, central mesenteric nodal, and abdominal wall lesions.

The Double Asteroid Redirection Test (DART) spacecraft was developed to provide the first measurement for orbital deflection of an asteroid upon intentional impact. The NEXT ion engine is part of the mission, on its maiden voyage. As part of the pre-launch risk reduction, erosion characteristics of the extraction grid system were evaluated using laser measurements of sputtered molybdenum atoms over the envelope of potential throttle conditions for the mission. Erosion rate dependence on propellant flow rate as well as relative density and directionality of molybdenum sputter from grid center to edge were measured. Sputtered atoms were found to have average radial velocity directed toward the engine perimeter and increasing with radial distance. The relative contribution of source and facility background gas and other sources of accelerator grid current was examined as well as the influence of several engine operating parameters. Facility background gas was found to influence engine operation more than a wall-mounted pressure gauge and typical assumptions about ingestion would indicate. Far-field flux was estimated over the full angular range based on the near-field relative density and velocity results and relying on quartz crystal microbalance data at one location to fix absolute numbers everywhere. The results substantially deepen knowledge and understanding of the complex grid erosion process of the engine and its lifetime, as grid failure via erosion is the normal life limiter. Study results are also relevant to thruster–spacecraft integration issues such as molybdenum deposition rate on solar cells and other spacecraft surfaces.

Summary: Events at a receptor ectodomain affect the intracellular domain conformation, activating signal transduction (out-to-in conformational effects). We investigated the reverse direction (in-to-out) where the intracellular domain may impact on ectodomain conformation. The primary sequences of naturally occurring TrkC receptor isoforms (TrkC-FL and TrkC.T1) only differ at the intracellular domain. However, owing to their differential association with Protein Disulfide Isomerase the isoforms have different disulfide bonding and conformations at the ectodomain. Conformations were exploited to develop artificial ligands, mAbs, and small molecules, with isoform-specific binding and biased activation. Consistent, the physiological ligands NT-3 and PTP-sigma bind both isoforms, but NT-3 activates all signaling pathways, whereas PTP-sigma activates biased signals. Our data support an “in-to-out” model controlling receptor ectodomain conformation, a strategy that enables heterogeneity in receptors, ligands, and bioactivity. These concepts may be extended to the many wild-type or oncogenic receptors with known isoforms.

Rosai-Dorfman disease is a rare subtype of non-Langerhans cell histiocytosis. With the last major report published in 1990, there is a paucity of contemporary data on this disease. Our objective was to report the clinicopathological features, treatments and outcomes of patients seen at a tertiary referral center. Sixty-four patients with histopathological diagnosis of Rosai-Dorfman disease were identified from 1994 to 2017 (median age 50 years; range, 2-79). The median duration from symptom onset to diagnosis was seven months (range, 0-128), which was also reflected in the number of biopsies required to establish the diagnosis (median 2; range, 1-6). The most common presentation was subcutaneous masses (40%). Of the 64 patients, 8% had classical (nodal only) and 92% had extra-nodal disease (67% extra-nodal only). The most common organs involved were skin and subcutaneous tissue (52%), followed by lymph nodes (33%). Three patients had an overlap with Erdheim-Chester disease, which had not been described before. Two of these were found to have MAP2K1 mutations. Commonly utilized first line treatments were surgical excision (38%) and systemic corticosteroids (27%). Corticosteroids led to a response in 56% of the cases. Of those treated initially, 15 (30%) patients developed recurrent disease. The most commonly used systemic agent was cladribine (n=6), with 67% overall response rate. Our study demonstrates that Rosai-Dorfman disease has diverse clinical manifestations and outcomes. While this disease has been historically considered a benign entity, a subset of patients endures an aggressive course necessitating the use of systemic therapies.

The F508 deletion (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. Here the authors show that cytosolic chaperones shift the F508del channel conformation to the native fold by kinetic and thermodynamic remodelling of the gating energetics towards that of wild-type CTFR.

The association between pulmonary hypertension (PH) and hypoxia is well-established, with two key mechanistic processes, hypoxic pulmonary vasoconstriction and hypoxia-induced vascular remodeling, driving changes in pulmonary arterial pressure. In contrast to other forms of pulmonary hypertension, the vascular changes induced by hypoxia are reversible, both in humans returning to sea-level from high altitude and in animal models. This raises the intriguing possibility that the molecular drivers of these hypoxic processes could be targeted to modify pulmonary vascular remodeling in other contexts. In this review, we outline the history of research into PH and hypoxia, before discussing recent advances in our understanding of this relationship at the molecular level, focussing on the role of the oxygen-sensing transcription factors, hypoxia inducible factors (HIFs). Emerging links between HIF and vascular remodeling highlight the potential utility in inhibiting this pathway in pulmonary hypertension and raise possible risks of activating this pathway using HIF-stabilizing medications.

Cystic Fibrosis is caused by mutations in the CFTR anion channel, many of which cause its misfolding and degradation. CFTR folding depends on the Hsc70 and Hsp70 chaperones and their co-chaperone DNAJA1, but Hsc70/Hsp70 is also involved in CFTR degradation. Here, we address how these opposing functions are balanced. DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by Hsc70/Hsp70 and the E3 ubiquitin ligase CHIP. Excess Hsp70 also promoted CFTR degradation, but this occurred through the lysosomal pathway and required CHIP but not complex formation with HOP and Hsp90. Notably, the Hsp70 inhibitor MKT077 enhanced levels of mature CFTR and the most common disease variant ΔF508-CFTR, by slowing turnover and allowing delayed maturation, respectively. MKT077 also boosted the channel activity of ΔF508-CFTR when combined with the corrector compound VX809. Thus, the Hsp70 system is the major determinant of CFTR degradation, and its modulation can partially relieve the misfolding phenotype.

It is not currently well-understood how much xylem conductance is lost in maize plants during the day, if conductance is recovered during the night, or what soil water conditions are required for recovery to take place. To answer these questions we designed a greenhouse experiment whereby two genetically dissimilar maize genotypes were subjected to a level of water stress commonly experienced in the field (Ψxylem ∼-2 MPa). We then measured the loss of stem-specific conductivity associated with this level of stress, as well as the overnight recovery following three re-watering treatments: Ψsoil ∼ 0 MPa, Ψsoil ∼-0.40 MPa, and Ψsoil ∼-1.70 MPa. Mid-day leaf water potentials of -1.98 MPa resulted in stem-specific conductivity (KS) values that were 31.5% of maximal (i.e., 68% loss). Returning soils to field capacity (Ψsoil ∼ 0 MPa) overnight allowed for the significant recovery of KS (76% of maximal), whereas partial watering (Ψsoil ∼-0.40 MPa) resulted KS values that were 51.7% of maximal values, whereas not watering resulted in no recovery (35.4% of maximal; Ψsoil ∼-1.7 MPa). Recovery of KS was facilitated by the generation of root pressure and low rates of nighttime transpiration.

Protein-folding diseases are an ongoing medical challenge. Many diseases within this group are genetically determined, and have no known cure. Among the examples in which the underlying cellular and molecular mechanisms are well understood are diseases driven by misfolding of transmembrane proteins that normally function as cell-surface ion channels. Wild-type forms are synthesized and integrated into the endoplasmic reticulum (ER) membrane system and, upon correct folding, are trafficked by the secretory pathway to the cell surface. Misfolded mutant forms traffic poorly, if at all, and are instead degraded by the ER-associated proteasomal degradation (ERAD) system. Molecular chaperones can assist the folding of the cytosolic domains of these transmembrane proteins; however, these chaperones are also involved in selecting misfolded forms for ERAD. Given this dual role of chaperones, diseases caused by the misfolding and aberrant trafficking of ion channels (referred to here as ion-channel-misfolding diseases) can be regarded as a consequence of insufficiency of the pro-folding chaperone activity and/or overefficiency of the chaperone ERAD role. An attractive idea is that manipulation of the chaperones might allow increased folding and trafficking of the mutant proteins, and thereby partial restoration of function. This Review outlines the roles of the cytosolic HSP70 chaperone system in the best-studied paradigms of ion-channel-misfolding disease – the CFTR chloride channel in cystic fibrosis and the hERG potassium channel in cardiac long QT syndrome type 2. In addition, other ion channels implicated in ion-channel-misfolding diseases are discussed.

To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.HIV-1 pol sequence data were analyzed to infer the local transmission network.We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p

Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR). BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology.

Insulin detemir is a long-acting basal insulin approved for use in patients with type 1 (T1DM) or type 2 diabetes (T2DM). Insulin detemir has demonstrated equivalent glycemic control and hypoglycemic risk when compared to insulin glargine, and insulin detemir has generally but not consistently demonstrated less weight gain than insulin glargine in T2DM. The benefits of basal insulin analogs relative to NPH insulin are well recognized, including less FBG variability, lower risk of hypoglycemia, and less weight gain specifically with insulin detemir. However, NPH insulin continues to be widely prescribed, which may be due in part to economic considerations. While NPH insulin generally costs less per prescription, insulin detemir has been shown to be cost effective compared to NPH insulin as well as insulin glargine. Therefore, insulin detemir is an effective option from both clinical and economic perspectives for patients with T1DM or T2DM who require basal insulin to achieve glycemic control.

A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites.